McLaglen was born in Tunbridge Wells, Kent, England. His father, a bishop, moved the family to South Africa when McLaglen was a child. He had four brothers who also became actors, Arthur (1888-1972), an actor and sculptor, and Clifford (1892-1978), Cyril (1899-1987), and Kenneth (c. 1901-1979).

Other siblings included Frederick (b. c1882), Sydney (b. ca1884), Lewis (b. ca1889), and a sister, Lily (b. ca1893). Another brother, Leopold McLaglen, who appeared in one film, gained notoriety prior to World War I as a showman and self-proclaimed World Ju-jutsu Champion, who authored a book on the subject.

He left home at fourteen to join the British Army with the intention of fighting in the Second Boer War. However, much to his chagrin, he was stationed at Windsor Castle with the Life Guards 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, in a 6 round exhibition bout.

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 I although he actually served as a Temporary Captain with the 10th Battalion, Middlesex Regiment, now part of the The Princess of Wales's Royal Regiment (Queen's and Royal Hampshires).

He served for a time as military Provost Marshal for the city of Baghdad. He also continued boxing, and was named Heavyweight Champion of the British Army in 1918. After the war, he began taking roles in British silent films.

McLaglen's career took a surprise 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, McLaglen 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. The episodes of those series in which McLaglen guest-starred were both directed by his son, Andrew V. McLaglen, who later was a film director.