
But this wasn't everyone's opinion. Harrison had represented Indiana in the United States Senate from 1881 to 1887, and had lost his re-election bid. Still, in February 1888, Harrison announced his candidacy for the Republican presidential nomination. He placed fifth on the first ballot at the 1888 Republican convention, with Sherman in the lead and the next few ballots showed little change. When the Blaine supporters shifted their support to Harrison, they found that his candidacy appealed to voters from other delegations and Harrison was nominated as the party's presidential candidate on the eighth ballot.
In the general election against incumbent President Grover Cleveland, Harrison used a traditional front-porch campaign, while Cleveland made only one public campaign appearance. The Republicans campaigned in favor of protective tariffs, attracting the support of protectionist voters in the important industrial states of the North. The election came down to the swing states of New York, New Jersey, Connecticut, and Harrison's home state of Indiana. Harrison and Cleveland split these four states, with Harrison winning in New York and Indiana. Although he received approximately 90,000 fewer popular votes than Cleveland, Harrison won the Electoral College vote 233 to 168. In the congressional elections, the Republicans increased their membership in the House of Representatives by nineteen seats, winning control of the house. The party also retained control of the Senate, giving one party unified control of Congress and the presidency for the first time since 1874.
Harrison was sworn into office on March 4, 1889. He was 5' 6" tall, and was the last president to sport a full beard. Harrison's inauguration ceremony took place during a rainstorm in Washington D.C. Grover Cleveland attended the ceremony and held an umbrella over Harrison's head as he took the oath of office. Harrison's speech was brief (half as long as that of his grandfather, William Henry Harrison, who holds the record for the longest inaugural address of a U.S. president - and the shortest term in office.) He called for the regulation of trusts (monopolies), safety laws for railroad employees, aid to education, and funding for internal improvements. Harrison also urged early statehood for the territories and advocated pensions for veterans, a proposal that was met with enthusiastic applause.
Harrison's cabinet choices did not make him very popular within his party. Although he had not personally made any promises to win his nomination as president, those working for him had, and there were political bosses within the party who expected to have their nominees appointed to the cabinet. Harrison did not live up to their expectations, and this would come to hurt him politically.
It was presumed that James G. Blaine would be given the post of Secretary of State, and while Harrison did so, he delayed the announcement in order to prevent Blaine from becoming involved in the planning of the new administration. Harrison was of the opinion that when Blaine was President James Garfield's incoming Secretary of State, Blaine had held too much power in choosing the personnel of the Garfield administration. Harrison wanted to be his own man, without influence from Blaine. In spite of this however, Blaine and Harrison agreed on most major policy issues, and Blaine went on to play a major role in Harrison's administration. Blaine remained as Secretary of State throughout Harrison's term until poor health forced his resignation from the cabinet in 1892. Blaine was replaced by John W. Foster, an experienced diplomat.
For the important position of Secretary of the Treasury, Harrison offended Thomas C. Platt and Warner Miller, two powerful New York Republicans who fought for control of their state party. He rejected their proposed nominees and instead chose William Windom, a Minnesotan who lived in New York and who had served in the same job during the Garfield administration. Windom died in January of 1891 and was succeeded by former Governor Charles Foster of Ohio.
It was expected that New York Republicans would have a place in cabinet and Harrison did appoint Benjamin F. Tracy, but to the minor position of Secretary of the Navy. Like Harrison, Tracy believed in a naval strategy focused more on offense, rather than on coastal defense and commerce raiding. He was a disciple of naval theorist Captain Alfred Thayer Mahan, who had served as a professor at the new Naval War College (founded 1884). In 1890, Mahan published his major work, The Influence of Sea Power upon History, 1660–1783, the leading book of its era on the operation of a navy. Tracy suffered personal tragedy when in 1890 his wife and child died in a fire at their residence in Washington, DC. He remained in his cabinet position throughout Harrison's presidency.
Pennsylvania was another state whose boss, Matthew Quay, expected a member of his faction to be placed in a prominent cabinet post. He was disappointed when the state's only appointment in cabinet was Postmaster General John Wanamaker. Wannamaker was a prominent department store businessman. He was accused by local newspapers of buying his cabinet position, and his tenure at the Post Office was filled with controversy, including the firing of some 30,000 postal workers under the "spoils system" during his four-year term, which caused inefficiency and a run-in with civil-service crusader Theodore Roosevelt, a fellow Republican.
The position of Secretary of the Agriculture had been created during the end of Cleveland's first presidency. Harrison appointed Wisconsin Governor Jeremiah M. Rusk to this post. Rusk had gained notoriety as governor of his state for sending in the national guard to quell a strike in Milwaukee, leading to an incident known as the Bay View Tragedy. The guard fired into a crowd that included women and children, and seven people were killed, including a thirteen year old boy.
The Department of the Interior was reputed for its corruption when Harrison inherited the presidency. To address the problem, he appointed John Noble, a railroad attorney with a reputation for honesty and incorruptibility, to head the Department.
Harrison selected Redfield Proctor, a native of Vermont, as Secretary of War. Proctor played a key role in Harrison's nomination. At the War Department, Proctor was praised for his managerial skill and efficiency, and for modernizing the Army and improving the living conditions of enlisted soldiers. Proctor resigned this position in 1891 to take a Senate seat, and was replaced by Stephen B. Elkins, formerly of New Mexico, and later a prominent businessman in West Virginia.
As Attorney-General, Harrison chose his close friend and former law partner, William H. H. Miller.
Senator Shelby Cullom of Illinois summed up Harrison's dislike of the use federal positions for patronage, when he said: "I suppose Harrison treated me as well as he did any other Senator. But whenever he did anything for me, it was done so ungraciously that the concession tended to anger rather than please." Harrison held two full cabinet meetings per week, as well as separate weekly one-on-one meetings with each cabinet member.

Harrison's refusal to play the Washington DC political game of "you scratch my back and I'll scratch yours" contributed to his failure to win re-election in 1892. The treasury surplus had evaporated and the nation's economic health was getting worse. This would eventually lead to the Panic of 1893. Although Harrison had worked with Congressional Republicans on legislation, several party leaders withdrew their support for him because of his adamant refusal to give party members a say in his executive appointments. Party bosses Matthew Quay (of Pennsylvania), Thomas Platt (of New York), and Speaker of the House Thomas Reed of Maine quietly organized a group that became known as "the Grievance Committee" to start a dump-Harrison movement. They were soon joined by James G. Blaine. Despite this, Harrison resolved to run for re-election. Some party leaders still hoped to draft Blaine into running, but at the convention in Minneapolis, Harrison prevailed on the first ballot.
The Democrats renominated former President Cleveland, making the 1892 election a rematch of the one four years earlier. The tariff revisions of the past four years had made imported goods so expensive that now many voters now favored lowering the tariff. The Populist Party held its first national convention in July, nominated a presidential ticket led by former Congressman James Weaver of Iowa. Many traditionally Republican Westerners defected to Weaver. The effects of the suppression of a number of labor strikes caused many Northern laborers to defected to the Democrats.
During the campaign of 1892, Harrison's wife Caroline waged a battle with tuberculosis and two weeks before the election, on October 25, she died. Harrison suspended his campaign, and to his credit, so did Grover Cleveland out of respect (though by this point, his victory was a foregone conclusion.) Cleveland ultimately won the election by 277 electoral votes to Harrison's 145, the most decisive margin in 20 years. Cleveland won 46% of the popular vote, beating Harrison by a margin of approximately 375,000 votes. Cleveland swept the four swing states of New York, New Jersey, Connecticut, and Indiana, and also became the first Democrat since the Civil War to carry Wisconsin and Indiana. Weaver received just over one million voters and twenty-two electoral votes, with most of his support coming from Western voters.