David Mills was born 18 March 1831 in Orford Township, Upper Canada, to Nathaniel Mills and Mary Guggerty. David received his early education at the local school in Palmyra Corners. He became a teacher and from April 1856 to April 1865 he served as a school superintendent in Kent. He married Mary Jane Brown on 17 December 1860 in Chatham, Upper Canada, and had three sons and four daughters. During this time spent as superintendent he also farmed on his inherited part of the family farm at Palmyra. By 1864 he seems to have become active politically in the Reform party in Kent.
In 1865 he enrolled at the University of Michigan Law School from which he graduated in March of 1867. Mills attained his degree but made no formal application to the law society until 1878, and he was not called to bar until 1883. He first practiced law in the firm of Ephraim Jones Parke in London, Ontario and later practiced with one of his sons. In 1885 he was on the faculty of the newly opened London Law School as professor of international law and the rise of representative government. Five years later he became a Queen's Council lawyer.
After graduating from the University of Michigan in 1867, Mills returned to Canada and secured the Reform nomination for the federal constituency of Bothwell, which covered parts of Kent and Lambton counties. He would hold the seat until 1882 and again from 1884 to 1896. He introduced a motion to do away with the practice of dual representation at the federal level on 20 November 1867 and had it completely abolished in 1873. In 1872 he suggested that senators be properly elected or chosen directly by the provincial legislatures, and remained an advocate for the Senate to be rendered a better guardian of provincial interests. Mills told parliament in June 1869 that if ever it was "a question whether Federal or Local Legislatures should be destroyed," his view was that "the country would suffer far less by the destruction of the Federal power."
In 1872 he asked Oliver Mowat, the Liberal premier of Ontario from 1872 to 1896, to prepare a written defense of the province's placement of its disputed western and northern boundaries. The report was published in early 1873 and made Mills a key player in the boundary dispute. Mills was asked in January 1876 to chair the select committee established to investigate the economic depression and was appointed minister of the interior in October.
The defeat of the Mackenzie government in the election of 1878 put an end to Mills' ministerial duties and administrative ambitions. He retained Bothwell, however, making him one of the senior Ontario Liberals in the caucus. He was one of the leaders of the movement in 1880 to oust Mackenzie from the leadership position. Mills became one of Edward Blake's chief lieutenants when he became leader and coordinated the Liberal filibuster in 1885. He considered his speech of 1 April 1885 to be one of the finest speeches of his parliamentary career.
As editor-in-chief of the London Advertiser from 1882 to 1887, Mills built a case against the Macdonald government's administration of national affairs in a series of unsigned, but distinctive, editorials. He seems to have been particularly active as a journalist in 1883, when he was defeated in the election of 20 June 1882 and was forced to sit out a session of parliament while his case was considered by the courts. He won in February 1884 and returned to the commons. In 1886 he followed Blake in condemning the execution of Louis Riel and in 1889 he delivered a strong speech opposing disallowance, arguing that parliament had no business interfering with legislation that was clearly within provincial jurisdiction. In the 1890 debate over the use of French in legislature, Mills delivered an eloquent speech in defense of linguistic rights.
Mills lost Bothwell in the general election of 23 June 1896. Although summoned to the Senate in November 1896, he was not invited to join the cabinet. He consequently devoted more time to his law practice in London, continued his work at the University of Toronto, where he had been appointed in 1888 to teach constitutional and international law, and wrote and lectured on a wide variety of religious and political subjects. Laurier asked Mills to fill the vacancy left by Sir Oliver Mowat in 1897 and on 18 November he was sworn in as minister of justice and became government leader in the Senate.
In 1902 Mills arranged his own appointment as a puisne judge of the Supreme Court of Canada, a move that was widely criticized. On 8 May 1903, Mills died suddenly of an internal haemorrhage, leaving behind his wife and six of his children.