McLaglen was born in Tunbridge Wells, Kent, England. His father, a bishop, moved the family to South Africa when McLaglen was a child. He left home at fourteen to join the army with the intention of fighting in the Second Boer War. However much to his chagrin, he was stationed at Windsor Castle and was later forced to leave the army when his true age was discovered.

Four years later, he moved to Canada, where he earned a living as a wrestler and heavyweight boxer, with several notable wins in the ring. One of his most famous fights was against Heavyweight Champion Jack Johnson. The fight was a 6 round "No contest" bout which meant that the only way to win was by a knockout prior the bell to end the 6th round. McLaglen survived all 6 rounds and a no contest was declared. Between bouts, he toured with a circus, which offered $25 to anyone who could go three rounds with him. He returned to England in 1913 and claimed to have served with the Royal Irish Fusiliers during World War 1 although no records contain his name {See following note for war service . He also continued boxing, and was named Heavyweight Champ of the British Army in 1918. After the war, he began taking roles in British silent films.

McLaglen's career took a turn in the 1920s, when he moved to Hollywood. He became a popular character actor, with a particular knack for playing drunks. The highlight of his career was an Academy Award for Best Actor for his role in The Informer (1935), based on a novel by Liam O'Flaherty. Near the end of his career he was nominated again, this time for Best Supporting Actor, for his role opposite John Wayne in The Quiet Man (1952). He was especially popular with director John Ford, who frequently included McLaglen in his films. Toward the end of his career, McLaglen made several guest appearances on television, particularly in Western series such as Have Gun, Will Travel and Rawhide.

He died of a heart attack in 1959. He had by that time become a naturalized U.S. citizen. His son, Andrew McLaglen was a director.