Mitchell's father took him at the age of five to a farm in the neighboring Butler County where he attended a rural school. At seventeen, he began teaching during the winter while in the other months of the year he studied at Butler Academy and afterward also at Witherspoon Institute. He then read law and was admitted to its practice in 1857 at Butler, Pennsylvania.
Under the name of Mitchell, he took up the practice of law, during his first year was appointed a city attorney, and in his second year was elected a member of the city council. With the outbreak of the Civil War he supported the Unionist cause, helped to defeat the movement to form at that time a "Pacific Coast Republic, " and in 1862 was elected to the state Senate as a candidate of the Unionist party. Reelected to that body in 1864, he was made its president and in 1866 came within one vote of being elected United States senator, an election won in 1872 against Henry W. Corbett. In the meantime, he had built up a lucrative law practice, associated, 1862-83, with Joseph N. Dolph and aided by his connection with Ben Holladay, who dominated river and railroad transportation in Oregon, and whose interests in the Oregon legislature Mitchell defended. After his election as senator in 1872, the Democratic opposition brought up against him his Pennsylvania "past" in an effort to prevent him from taking his seat. The story of his private life continued to come up in succeeding campaigns, but more detrimental to his political success was the opposition of the Corbett group and of Harvey W. Scott, editor of the Portland Morning Oregonian and a rival for the leadership of the Republican party in the state, who came to oppose bitterly Mitchell's successive attempts to be reëlected United States senator.
The attacks in the Oregonian became more virulent after Mitchell had caused Scott's removal in 1876 as customs' collector at Portland. In 1878, a Democratic majority in the legislature brought about the election of James H. Slater to succeed him as a senator, and in 1882, unable to secure his own election, he threw his vote to his law partner, Dolph, who was ultimately elected. The regular legislative session of 1885 adjourned without the election of a senator, but at a called session Mitchell was a second time elected, Nov. 18, 1885. Seventeen Democrats voted for him after the Oregonian had printed facsimile letters written by Mitchell, showing marital infidelity, and charged that his conduct in the United States Senate had been "as grossly mercenary and corrupt" as his private life had been immoral. Later it was charged that he had bought the votes necessary to his election with money furnished by the Southern Pacific Railroad. He had, however, a large and devoted following and he was reëlected in 1891 without Republican opposition. He failed of reëlection in 1897 because his stand on the money question had satisfied neither gold nor silver men. In 1901 he was for the fourth time elected United States senator. In July 1905, he was convicted in the United States district court on an indictment of having received fees for expediting the land claims of clients before the United States Land Commissioner, a charge that the evidence, as presented by special prosecutor Francis J. Heney, seemed amply to sustain. His death came pending an appeal. The Senate departed from its usual custom in honoring a deceased member by refusing either to adjourn or to send a delegation to attend his funeral.
Mitchell was adroit in championing the popular will on questions of public interest. He supported the interstate commerce, the Sherman silver purchase, and Chinese exclusion acts in the Senate. He gave his approval to the "Oregon system" of an initiative, referendum, and direct primary; supported woman's suffrage, and made capital of the opposition of the Oregonian by representing himself as the candidate of the people against the conservative and business interests.
Mitchell was charged with having deserted his family in Pennsylvania, with financial dishonesty, with bigamy, and with living under an assumed name, charges which the Senate committee on privileges and elections decided (June 27, 1874) did not merit investigation. Mitchell, however, felt compelled to make a reply to this attack in a public letter in which he protested his innocence. He did, however, secure a divorce from his first wife and legalize the change in his name by an act of the Multnomah County court in 1874.
Mitchell was married to Sadie Hoon whom he left behind with their two children, when he went to California in 1860. In 1862, he had married Mattie Price of Oregon City without securing a divorce from his first wife. There were six children in his Oregon family.