McLean was born in Morris County, New Jersey, the son of Fergus McLean and Sophia Blackford. After living in a succession of frontier towns, Morgantown, Virginia; Nicholasville, Kentucky; and Maysville, Kentucky; in 1797 his family settled in Ridgeville, Warren County, Ohio. His brother William was also a successful Ohio politician.

He studied law and was admitted to the bar in 1807. That same year he founded The Western Star, a weekly newspaper at Lebanon, the Warren County seat, where he practiced law. He was elected to the U.S. House for the Thirteenth and Fourteenth Congresses, serving from March 4, 1813, until he resigned in 1816 to take a seat on the Ohio Supreme Court which he had been elected to February 17, 1816, replacing William W. Irwin.

He resigned his judgeship in 1822 (Charles Robert Sherman replaced him on the court) to take President James Monroe's appointment to be Commissioner of the General Land Office, serving until 1823, when Monroe appointed him United States Postmaster General. McLean served in that post from December 9, 1823, to March 7, 1829, under Monroe and John Quincy Adams, presiding over a massive expansion of the Post Office into the new western states and territories and the elevation of the Postmaster Generalship to a cabinet office. While Postmaster General, he supported Andrew Jackson, who offered him the posts of Secretary of War and Secretary of the Navy, but he declined both and was instead appointed to the Supreme Court.

Known as "The Politician on the Supreme Court," he associated himself with every party on the political spectrum, moving from a Jackson Democrat, to the Anti-Jackson Democrats, the Anti-masonic Party, the Whigs, the Free Soilers, and finally the Republicans. President John Tyler again offered the post of Secretary of War, but he declined. Because of his fierece anti-slavery positions, he was considered by the new Republican party as a candidate in 1856. Despite his efforts, the nomination went to John C. Frémont. In 1860, he tried again, winning twelve votes on the first ballot at the Republican convention in Chicago; Abraham Lincoln ultimately was nominated.

In Dred Scott v. Sanford, his fierce dissenting views are believed to have forced the hand of Chief Justice Roger Brooke Taney into a harsher and more polarizing opinion than he originally planned. He also wrote the Court's opinion denying there was a common-law copyright in American law in Wheaton v. Peters.

He died in Cincinnati, Ohio and was buried in Spring Grove Cemetery, Cincinnati.