In October, 1864, while at the front, he was re-elected, by 19,713 majority, reporter of the Supreme Court, which office he had lost by accepting a commission in the army. After four years as reporter he resumed his law practice, forming a partnership with Albert G. Porter and W. P. Fishback. About 1870 Mr. Fishback retired, and the firm became Porter, Harrison & Hines; upon Governor Porter's retirement W. H. H. Miller took his place, and in 1883 Mr. Hines retired, and, John B. Elam coming in, the firm became Harrison, Miller & Elam.
In 1876 Hon. Godlove S. Orth was nominated as Republican candidate for Governor of Indiana, but pending the canvass he unexpectedly withdrew. In this emergency, during General Harrison's absence on a trip to Lake Superior, the Central Committee substituted his name at the head of the ticket. Undertaking the canvass despite adverse conditions, he was defeated by Hon. James D. Williams—"Blue Jeans"—by a plurality of 5,084 votes.
In 1878 he was chosen chairman of the Republican State Convention.
In 1879 he was appointed by President Hayes a member of the Mississippi River Commission.
In 1880 he was chairman of the delegation from Indiana to the National Convention, and with his colleagues cast 34 consecutive ballots for James G. Blaine in that historic contest.
President Garfield tendered him any position but one in his Cabinet, but the high honor was declined.
In January, 1881, he was elected United States Senator—the unanimous choice of his party—to succeed Joseph E. McDonald, and served six years to March 3, 1887.
In 1884 he again represented his State as delegate at large to the National Convention.
January, 1887, he was a second time the unanimous choice of his party for United States Senator, but after a protracted and exciting contest was defeated on the sixteenth joint ballot, upon party lines, by 2 majority.
June 25, 1888, he was nominated at Chicago by the Republican National Convention for President, on the eighth ballot, receiving 544 votes against 118 for John Sherman, 100 for Russell A. Alger, and 59 for Walter Q. Gresham. He was chosen President by 233 electoral votes against 168 for Grover Cleveland. The popular vote resulted: 5,536,242 (48.63 per cent.) for the Democratic ticket, 5,440,708 (47.83 per cent.) for the Republican ticket, 246,876 (2.16 per cent.) for the Prohibition, 146,836 (1.27 per cent.) for the Union Labor, and 7,777 (0.11 per cent.) scattering.