He was born in the village of Endicott, New York, the second son of Italian immigrant parents. From the age of six, George dreamed of being in films. After serving in World War II, George moved to Hollywood. Though the first few years were lean, by 1950, he had received his first credit and the work began to accumulate. The vast majority of George's roles were on television.

In 1955, George appeared as Sergei in the episode "Mightier Than the Sword" of the religion anthology television series, Crossroads, based on stories about American clergymen. He guest-starred in an episode of the syndicated television series, the sitcom, How to Marry a Millionaire, with Barbara Eden and in the first Brian Keith series, Crusader, a 1955–1956 Cold War drama which aired on CBS.

George was cast as an Indian guide in the 1956 episode "Death in the Snow" of NBC's anthology series, The Joseph Cotten Show: On Trial; Cotton later returned the favor, guest-starring in the episode "Face in the Window" of Checkmate. George portrayed Indian roles in the CBS western series, Brave Eagle, starring Keith Larsen as a young Cheyenne chief who tries to maintain peace with the white community. George was cast in the episodes "The Treachery of At-Ta-Tu" (1955), as Night Wind in "Voice of the Serpent" (1955), and as Red Wing in "Witch Bear" (1956).

On July 31, 1957, George was cast as Nick Frazee, a bank robber who kills a deputy sheriff before making his getaway, in the episode "Hold Up" of the syndicated crime drama, Sheriff of Cochise. Sheriff Frank Morgan (John Bromfield), based in Cochise County in Arizona, establishes roadblocks in pursuit of Frazee and two of his men, but the fleeing bandits take an isolated road into the mountains.

In 1958, Anthony George played an escaped mental patient in an episode of Highway Patrol, a police drama starring Broderick Crawford. (The first name of George's acting credits is sometimes Anthony, sometimes Tony.)

Later in 1959, at the age of thirty-eight, George was cast as federal agent Cam Allison in the first season of ABC's The Untouchables, with Robert Stack. He left that series when he landed his role on Checkmate, but The Untouchables outlasted Checkmate by a total of two years. Checkmate was George's most successful series. After Checkmate, George appeared in the lead in "The Johnny Masters Story" on another ABC western, Wagon Train.

George's longest-running success came from his decades-long career in daytime television soap-operas. In 1967, George replaced Mitchell Ryan as the brooding Burke Devlin on Dark Shadows. Some months later, the character was "killed" in a plane crash, and George created the role of Jeremiah Collins in a flashback to the year 1795. The story ran for most of 1967, until Jeremiah was killed off. George obtained further roles on CBS's Search for Tomorrow (as Dr. Tony Vincente, 1970–1975) and One Life to Live, the latter as Dr. Will Vernon #3.

In the late 1970s and early 1980s, One Life to Live was written and produced by many Dark Shadows alumni, which led to a scene where former Dark Shadows stars George, Nancy Barrett, and Grayson Hall, as their Llanview counterparts, wondered where they had previously met.

After being written out of One Life to Live in 1984, George continued to make sporadic film and television appearances. In 1988, he played the role of Alex Karides in "Baja, Humbug" in the CBS crime drama, Simon and Simon.

In 1991, George was awarded a Bronze Star on the Sidewalk of Stars in Binghamton, New York, close to Endicott, where he was born and raised.

George died of emphysema in 2005, aged 84, in a hospital in Newport Beach, Orange County, California.