Macklin first appeared as an actor at Bristol and in 1725 went to Lincoln's Inn Fields, London. A man of violent nature, he was a pioneer against the stilted declamation of his day. He went to Drury Lane Theatre in 1733 and later was concerned in its management. In 1735 he killed another actor in the greenroom over a dispute about a wig, but, although prosecuted, he received no sentence. He set the seal on his stage career at Drury Lane on Feb. 14, 1741, when he played Shylock, rescuing the part from the broad comedy with which it had long been surrounded.

Macklin played many parts with distinction but was constantly involved in disputes and lawsuits. He attempted to be a restaurateur but failed and returned to the stage. Two of his plays were outstanding, Love à la mode (1759) and The Man of the World (1781). At the time of his death, he claimed to be 107 years old; he may have been a centenarian, but this is subject to dispute. The length of his association with the stage, however, unquestionably made him a pillar of the English theatre.