He then attended the University of Michigan School of law, graduating with honors in 1867 with an Bachelor of Laws degree.
Mills served as superintendent of schools for Kent County from 1856 to 1865. He published The Present and Future Political Aspects of Canada in 1860 and The Blunders of the Dominion Government in connection with the North-West Territory in 1871. He returned to Parliament through an 1884 by-election.
He was re-elected in subsequent elections until his defeat in the 1896 election despite this being the election that brought the Liberals back to power.
He served as Minister of the Interior in the Cabinet of Alexander Mackenzie from 1876 to 1878. Sir Wilfrid Laurier appointed Mills to the Canadian Senate after he lost his Commons seat in 1896, and appointed him to Cabinet as Minister of Justice and Leader of the Government in the Canadian Senate.
He resigned from the Senate and Cabinet in 1902. He was appointed to the Supreme Court of Canada on February 8, 1902, and served on the Court for one year until his death in 1903.
Mills was first elected to the Canadian House of Commons as a Liberal Member of Parliament (Member of Parliament) in the 1867 federal election and re-elected in four subsequent votes until being defeated in the 1882 election.