Martin contracted polio in 1907. Martin was raised in Pembroke, Ontario, in the Ottawa River Valley, although he attended high school at Collège Saint-Alexandre in Gatineau, Quebec. He completed his university education at the University of Toronto, and earned his law degree from Osgoode Hall Law School. Later, Martin studied at the Graduate Institute of International Studies, Geneva, on a scholarship.

A member of the Liberal Party of Canada, he was first elected to the House of Commons in 1935 and entered the cabinet in 1945. He went on to serve as a noted member of the cabinets of four Prime Ministers: william Lyon Mackenzie King, Louis St. Laurent, Lester B. Pearson and Pierre Trudeau.

Martin was viewed as one of the most left-wing members of the Liberal cabinet, and as Minister of National Health and Welfare from 1946 to 1957 he played an important role in the fight against polio and overseeing the creation of hospital insurance in Canada, and is sometimes recognized as a father of medicare. Martin served as Secretary of State for External Affairs in the Pearson government, and was instrumental in the acquisition of U.S. nuclear weapons for Canadian Forces.

He ran for the Liberal leadership three times, in 1948, in 1958 and 1968, but was defeated at all three Liberal leadership conventions, first by Louis St. Laurent, then by Lester B. Pearson, then by Pierre Trudeau.

Trudeau appointed him to the Senate in 1968. He served as Leader of the Government in the Senate until 1974 when he was appointed High Commissioner to the United Kingdom. He also served as Chancellor of Wilfrid Laurier University from 1972–1977, as a result of which the university named the Paul Martin Centre in his honour. Until his death Paul Martin was an Adjunct Professor of Political Science at the University of Windsor.

In 1976 he was made a Companion of the Order of Canada. In recognition of his accomplishments, Martin was granted the right to use the honorific Right Honourable in 1992, a rare honour for one who has never been Prime Minister, Governor-General or Chief Justice of Canada.

His two volume memoirs, A Very Public Life, was published in 1983 (ISBN 0888790929) and 1986 (OCLC 165756245 A very public life: So many worlds Volume 2 of A very public life at Google Books).

The University of Windsor has a Paul Martin Chair in law and political science, recently held by former Manitoba Premier Howard Pawley (until his retirement from the University of Windsor), and the Paul Martin Law Library. The City of Windsor had also renamed their "Post Office Building" the Paul Martin Sr. Building in his honour on November 18, 1994.