He began his career on Broadway, but spent most of his professional life in the United Kingdom, where he emigrated after becoming fearful of being blacklisted in Hollywood due to his communist views in the 1950s.

Wanamaker became extensively involved in British theater, while continuing film and television work, eventually returning to some Hollywood productions while remaining based in the UK.

In 1952, at the height of the McCarthy "Red Scare" period, Wanamaker, who was then acting in the UK, learned that despite his distinguished service in the Army during World War II, his years as a communist could lead to his being blacklisted in Hollywood.

[7] In 1956, he directed the British premiere of Bertolt Brecht and Kurt Weill's musical play The Threepenny Opera (revived in New York in 1954 in a translation by Marc Blitzstein.

He brought a number of notable productions to the theatre, such as A View from the Bridge, Cat on a Hot Tin Roof, The Rose Tattoo and Bus Stop.

[7] In 1959, he joined the Shakespeare Memorial Theatre company at Stratford-upon-Avon, playing Iago to Paul Robeson's Othello in Tony Richardson's production that year.

Wanamaker eventually returned to Hollywood films including Private Benjamin (1980), Superman IV: The Quest for Peace (1987), and Baby Boom (1987).

He was nominated for a Primetime Emmy Award for Outstanding Supporting Actor in a Drama Series for his performance in the 1978 ABC television miniseries Holocaust.

In 1970 Wanamaker's career took a dramatic turn after he was annoyed that while a number of replicas of the Globe theatre existed in the United States, the site of the original in London was marked by only a plaque on a nearby brewery.

He found this neglect inexplicable, and in 1970 launched the Shakespeare Globe Trust, later obtaining the building site and necessary permissions despite a hostile local council.

When multi-Tony Award-winning British actor Mark Rylance accepted his third Tony on stage in New York City during the televised ceremonies on June 8, 2014, he did so with a note of thanks to Wanamaker.

In the 2014 memoir I Said Yes to Everything, Lee Grant claimed that during production of the film Voyage of the Damned (1976), Wanamaker engaged in an affair with British actress Lynne Frederick, who was 21 at the time.