Born in Los Angeles, he is one of John Wayne's four children by his first wife, Josephine Alicia Saenz, daughter of Panama's Consul General to the U.S. He adopted his father's stage surname, Wayne. He made eleven movies with his father: Rio Grande (1950), The Quiet Man (1952), The Searchers (1956), The Alamo (1960), The Comancheros (1961), Donovan's Reef (1963), McLintock! (1963), The Green Berets (1968) and Big Jake (1971).

Patrick made his film debut at age 11 in his father's film Rio Grande. He followed that with films directed by family friend and iconic Director John Ford: The Quiet Man, The Sun Shines Bright (1953), The Long Gray Line (1955), Mister Roberts (1955) and The Searchers (1956).

From 1957 to 1958, Wayne appeared as Walter on the CBS sitcom Mr. Adams and Eve, starring Howard Duff and Ida Lupino as a fictitious acting couple living in Beverly Hills. Other television work included the baseball teleplay Rookie of the Year (1955), directed by John Ford and starring John Wayne, and Flashing Spikes (1962), a baseball television anthology installment directed by Ford and starring James Stewart, with John Wayne in an extended cameo role. Patrick Wayne played similar roles in both shows as baseball players.

Following high school, Patrick attended Loyola Marymount University, where he was a member of Alpha Delta Gamma fraternity; he graduated in 1961. During this time, he struck out on his own to star in his own film The Young Land (1959). Patrick enlisted in the United States Coast Guard in 1961. He supported his Father in The Alamo, Donovan's Reef, McLintock! and The Green Berets. He also appeared in Ford's sprawling epic Cheyenne Autumn (1964), as James Stewart's son in Shenandoah (1965), in An Eye for an Eye (1966), The Deserter (1971), and in a lead role in The Bears and I for Walt Disney (1974).

In 1966 at age 27, Wayne co-starred with Ron Hayes and Chill Wills in the 17-episode ABC comedy-western series The Rounders, based on the 1965 Glenn Ford and Henry Fonda film of the same name. Patrick also served a tour of duty with the United States Coast Guard.

He had many appearances on popular television seriess of the 1970s and 1980s, including Fantasy Island (1978), Murder, She Wrote (1984), Charlie's Angels (1976), Sledge Hammer! (1986), and The Love Boat. Wayne appeared in the movie Young Guns (1988) as Pat Garrett. He also did a comic turn in the Western spoof Rustler's Rhapsody (1985) starring Tom Berenger.

Wayne served as the host of the 1990 revival of the game show Tic-Tac-Dough.

In 2003, Patrick became chairman of the John Wayne Cancer Institute.

In December 2, 2015, he travelled to Spain to receive the prize "Almeria Tierra de Cine" in Almeria (Andalucia) for his long career in the cinema, and he remembered his maternal grandparents were born in Madrid and he is half Spanish. He currently lives in Arizona.