
Breckinridge was born at Thorn Hill, his family's estate near Lexington, Kentucky, on January 16, 1821, the fourth of six children and the only son. His grandfather, also named John Breckinridge, served in the U.S. Senate and as Attorney General under President Thomas Jefferson. On February 25, 1841, he received a bachelor of laws degree and was licensed to practice law the next day. He decided that Lexington, Kentucky was overcrowded with lawyers, so he moved around, relocating to the Iowa Territory in October 1841. He found the bar stocked with able men like Stephen A. Douglas and Abraham Lincoln so he moved to Burlington, Iowa, where he prospered as a lawyer. There he joined the Democratic Party.
Breckinridge visited Kentucky in May 1843, and he Mary Cyrene Burch. By September, they were engaged. He went to Iowa to close out his business, then returned to Kentucky and formed a law partnership with Samuel Bullock. He and Mary were married on December 12, 1843, and they settled in Georgetown, Kentucky. The couple had six children. Gaining confidence in his ability as a lawyer, Breckinridge moved his family back to Lexington in 1845 and formed a partnership with future U.S. Senator James B. Beck.
During the Mexican–American War, Breckinridge applied to join the staff of General William O. Butler, but Butler could only offer an unpaid aide position. He again applied for a military commission and on September 6, 1847, he was appointed as major of the Third Kentucky Regiment. The regiment left Kentucky on November 1 and reached Vera Cruz in three weeks. Breckinridge walked all but two days of the journey, allowing weary soldiers to use his horse. When the soldiers reached Mexico City on December 18, the fighting was almost over and they participated in no military action, remaining in the city as an army of occupation until May 30, 1848.
While in Mexico, Breckinridge acted as counsel for Gideon Pillow in the court martial proceedings initiated against Pillow by General Winfield Scott. His role in the proceedings was limited to questioning a few witnesses as Pillow represented himself during the court's proceedings. Breckinridge had campaigned for Democrat James K. Polk during the 1844 campaign. In the 1848 presidential election, he backed the Democratic ticket of Lewis Cass and William Butler.
Breckinridge, was a slave owner who was opposed to abolition. He was a cousin of Mary Todd Lincoln and met Abraham Lincoln through her. Despite their political differences, the two became friends. Breckinridge served in the US House of Representatives from 1851 to 1855. Some Democrats proposed Breckinridge for Speaker of the House, but he refused to allow his name to be put in nomination. When he was home from the legislative session, Breckinridge made daily visits with the ailing Henry Clay. He was chosen to deliver Clay's eulogy in Congress when the next session commenced. He also campaigned for the election of Democrat Franklin Pierce as president. Pierce offered Breckinridge an appointment as governor of Washington Territory, but he decided to stay in Kentucky and seek re-election to the House. Following his re-election, he supported Pierce's pro-slavery agenda on the principle of states' rights and believed that secession was legal, but he opposed secession and was considered to be a moderate legislator. He supported the Kansas–Nebraska Act, incorrectly believing that passage of the act would remove the issue of slavery from national politics. During its debate on the House floor, a disagreement with New York's Francis B. Cutting led to what almost became a duel, but mutual friends resolved the issue. In 1854 Breckinridge decided to retire from the House at the expiration of his term.
Breckinridge returned to his law practice in Lexington. He was a delegate to the 1856 Democratic National Convention in Cincinnati, Ohio, and supported Pierce's re-nomination for president. When James Buchanan won the nomination, Breckinridge was nominated as the Democratic candidate for Vice-President and he helped the Democrats carry his home state of Kentucky in the election which the Democrats won. Thirty-six years old at the time of his inauguration on March 4, 1857, Breckinridge was the youngest vice-president in U.S. history, exceeding the minimum age required under the Constitution by only a year.
Buchanan resented the fact that Breckinridge had supported both Pierce and then Stephen Douglas before endorsing his nomination. Relations between the two were strained and Buchanan rarely consulted Breckinridge when making patronage appointments. At the end of his term, Breckinridge was appointed to fill a US Senate vacancy in Kansas. Breckinridge was touted as a potential candidate for the Democratic presidential nomination. Stephen Douglas was considered the frontrunner for the nomination. At the 1860 Democratic National Convention in Charleston, South Carolina, over the course of 57 ballots, Douglas maintained a wide plurality, but failed to gain a majority. Unable to nominate a candidate, delegates voted to reconvene in Baltimore, Maryland on June 18, 1860.
Pro-Southern delegates walked out of the Charleston convention in protest of its failure to adopt a federal slave code plank in its platform. They did not participate in the Baltimore convention. The protesting delegates convened five days later in Baltimore and selected Breckinridge as their candidate for President. He accepted the nomination. Breckinridge supporters believed his best hope was for the election to be thrown to the House of Representatives.
In a four-way contest, Breckinridge came in third in the popular vote, with 18.1%, but second in the Electoral College. The final electoral vote was 180 for Lincoln, 72 for Breckinridge, 59 for Bell, and 12 for Douglas. Breckinridge also carried the border states of Maryland and Delaware. He lost to Douglas in Missouri and Bell in Virginia and Tennessee. Bell also captured Breckinridge's home state, Kentucky. Lincoln swept most of the northern states, although New Jersey split its electoral votes, giving four to Lincoln and three to Douglas. On February 24, 1860, Breckinridge visited Lincoln at Willard's Hotel in Washington, D.C., and frequently thereafter, he visited his cousin, now the First Lady, at the White House. In the lame duck session following the election, Breckinridge used his influence in an unsuccessful attempt to try to reach a compromise that would avert secession.
Seven states had already seceded when Breckinridge took his seat as a senator, leaving him almost alone in his defense of slavery. Seeking to find a compromise that would reunite the states under constitutional principles, he urged Lincoln to withdraw federal forces from the Confederate states in order to avert war. On April 12, Confederate troops fired on Fort Sumter. In the senate Breckinridge was regarded as a traitor by most of his fellow legislators because of his Confederate sympathies. He condemned as unconstitutional Lincoln's enlistment and arming of men for a war Congress had not officially declared, his expending funds for the war that had not been allocated by Congress, and his suspension of the writ of habeas corpus. He was the only senator to vote against a resolution authorizing Lincoln to use "the entire resources of the government" for the war. Asked what he would do if he were president, he replied, "I would prefer to see these States all reunited upon true constitutional principles to any other object that could be offered me in life...But I infinitely prefer to see a peaceful separation of these States than to see endless, aimless, devastating war, at the end of which I see the grave of public liberty and of personal freedom."
In early September 1861, word reached Breckinridge that Union General Thomas E. Bramlette intended to arrest him. In an open letter to his constituents dated October 8, 1861, Breckinridge said that the Union no longer existed and that Kentucky should be free to choose her own course. He defended his sympathy to the Southern cause. On December 2, 1861, he was declared a traitor by the United States Senate. A resolution stating "Whereas John C. Breckinridge, a member of this body from the State of Kentucky, has joined the enemies of his country, and is now in arms against the government he had sworn to support: Therefore--Resolved, That said John C. Breckinridge, the traitor, be, and he hereby is, expelled from the Senate," was adopted by a vote of 36–0 on December 4.

On the recommendation of General Simon Bolivar Buckner, Breckinridge was commissioned as a brigadier general in the Confederate Army on November 2, 1861. His troops fought at the Battle of Shiloh on April 6, 1862. Although the Union won the battle, Breckinridge's performance earned him a promotion to major general on April 14, 1862. His troops also fought at Murfreesboro. He strongly disagreed with the tactics of General Braxton Bragg and in May 1863, Breckinridge was reassigned to the command of General Joseph E. Johnston, participating in the Battle of Jackson in an attempt to break the Siege of Vicksburg. Vicksburg fell to Grant's forces on July 4, and Breckinridge was returned to Bragg's command on August 28, 1863. His men fought at the Battle of Chickamauga and in the unsuccessful defense of Chattanooga, where his son, Cabell, was captured in the battle. Braxton Bragg charged Breckinridge with drunkenness and on December 15, 1862, Breckinridge took leave in Richmond. Confederate leaders were skeptical of Bragg's claims against Breckinridge, and in February 1864, Confederate President Jefferson Davis assigned him to the Eastern Theater. On May 5, 1864 Robert E. Lee ordered Breckinridge to take command of a reconnaissance mission to scout the federal forces under Franz Sigel near Winchester, Virginia. With a force of about 4,800 men, including 261 cadets from the Virginia Military Institute, he defeated Sigel's 6,300 men at the Battle of New Market. Subsequently he reinforced Lee's Army of Northern Virginia and played an important role in halting Grant's advance at the Battle of Cold Harbor. Breckinridge was wounded when a cannonball struck his horse and he was pinned underneath.
Breckinridge joined forces with General Jubal Early in a considered raid on Washington, D.C. After the Battle of Fort Stevens, Early decided to withdraw rather than assault the well-fortified federal capital. Abraham Lincoln watched the fight from the ramparts of Fort Stevens, the only time in American history when two former opponents in a presidential election faced one another across battle lines.
James A. Seddon resigned as the Confederate Secretary of War on January 19, 1865, and Confederate President Jefferson Davis appointed Breckinridge to the vacant position. His first act as secretary was to promote Robert E. Lee to general-in-chief of all Confederate forces. But by late February, Breckinridge concluded that the Confederate cause was hopeless and he began laying the groundwork for surrender. Davis desired to continue the fight, but Breckinridge urged, "This has been a magnificent epic. In God's name let it not terminate in farce." On April 2, Lee sent a telegram to Breckinridge informing him that he would have to withdraw from his position that night, and that this would necessitate the evacuation of Richmond. Breckinridge remained in the city to oversee the destruction of facilities and supplies to prevent their use by the invading federal forces.
Following the surrender of Robert E. Lee on April 9, Breckinridge advised that the remaining Confederate armies also surrender. Only Davis and Secretary of State Judah P. Benjamin disagreed. He assisted Joseph E. Johnston in his surrender negotiations with William T. Sherman.
By May 11, following the capture of Jefferson Davis, Breckinridge was the highest-ranking former Confederate official still at large. He decided to flee to the Bahamas, but strong winds the navigation of his small craft out to sea. Surviving an encounter with pirates, two significant storms, and a dangerous lack of provisions, he and his fellow travelers arrived at Cardevas in Cuba on June 11, 1865. The next morning, they traveled by rail to Havana. From there he traveled to Great Britain in late July where he arranged communication with his wife, then in Canada. Re-crossing the Atlantic, he was reunited with his wife and most of his children in Toronto on September 13, 1865. The family later journeyed to Europe, where the children attended school in Paris, Versailles, and Vevey, Switzerland. From mid-1866 to early 1868, Breckinridge toured Europe – including visits to Germany, Austria, Turkey, Greece, Syria, Egypt, and the Holy Land. During their tour of Italy, Breckinridge met with Pope Pius IX in Rome, and also visited Pompeii.

Desiring to return to the U.S. but still fearing capture, Breckinridge moved his family back to Niagara, Ontario in June 1868. On January 8, 1868, the Louisville City Council instructed the state's congressional delegation to seek assurance that Breckinridge would not be prosecuted on his return. President Andrew Johnson proclaimed amnesty for all former Confederates on December 25, 1868. Departing Canada on on February 10, he made several stops to visit family and friends along the route to Lexington, where he arrived on March 9, 1868. He resided in Kentucky for the rest of his life. In August 1868, he became manager of the Kentucky branch of Virginia's Piedmont Life Insurance Company. He resumed his law practice. In March 1870, he publicly denounced the actions of the Ku Klux Klan.
By 1873, Breckinridge began to experience health problems. In May 1875, surgeons diagnosed his ill health as being caused by cirrhosis brought on by injuries to his liver suffered during the war. Fluid filled two-thirds of one of his lungs, some of which was drained with surgery. On May 17, 1875 his condition rapidly worsened, and he died at approximately 5:45 p.m.