Born George Brendan Nolan in Shannonbridge, County Offaly, Ireland, to a family with a history of British Army service.

However, during the Anglo-Irish War (1919-1922), he was part of an IRA Active Service Unit as early as 1920 carrying out IRA directives. He fled with a price on his head by the British, although he first claimed that he had only been a courier for guerrilla leader and tactician, Michael Collins. He eventually moved to Hollywood where he made his first film in 1930.

Signed to a contract with Warner Brothers he acted for more than twenty years, establishing himself as a dependable but wooden actor, who was not a trained thespian, but a young man who fell into cinema (as an IRA fugitive from his homeland) because of his good looks and charm.

Highly regarded by Davis, notwithstanding the above, he became her most frequent male co-star (and one-time lover), appearing with her in twelve films, including Jezebel (1938), The Old Maid (1939), Dark Victory (1939) and The Great Lie (1941). He also played opposite Greta Garbo in The Painted Veil (1934), Madeleine Carroll in The Case Against Mrs. Ames (1936), Jean Arthur in More Than a Secretary (1936), Myrna Loy in The Rains Came (1939), Merle Oberon in 'Til We Meet Again (1940), Ann Sheridan in Honeymoon For Three (1941), Joan Fontaine in The Affairs of Susan (1945), Barbara Stanwyck in The Gay Sisters (1942) and My Reputation (1946), Claudette Colbert in Tomorrow is Forever (1946), Dorothy McGuire in The Spiral Staircase (1946), Lucille Ball in Lover Come Back (1946) and Yvonne De Carlo in Slave Girl (1947).

Brent's few starring roles failed to achieve success, and he drifted into "B" pictures from the late 1940s. He retired from acting in 1956 but made a return in 1978 in the made-for-television production Born Again.

Brent was known as a womaniser in Hollywood, and had a lengthy relationship with his co-star Bette Davis. He was married six times including three marriages to actresses - Ruth Chatterton (1932-1934), Constance Worth (1937) and Ann Sheridan (1942-1943). Chatterton and Sheridan were both fellow Warners Brothers players. Bette Davis recounted in her final years about what was her last meeting with Brent after many years of estrangement.

She expressed great remorse at his ill health (emphysema), and sadness that such a virile and attractive man could have deteriorated so dramatically.

He died shortly after in Solana Beach, California at the age of 80 from emphysema.