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). Patrick also served a tour of duty with the United States Coast Guard from 1961 to 1965.

Following work on his father’s 1971 film Big Jake, Wayne earned recognition in the sci-fi genre. His career peaked in the late 1970s in the popular matinee fantasy Sinbad and the Eye of the Tiger (1977), then in The People That Time Forgot (1977). Wayne also screen-tested for the title role of Superman. He co-starred as a romantic love interest to Shirley Jones in another brief TV series, Shirley (1979). He was the host of The Monte Carlo Show in 1980, and occasionally worked on game shows and syndicated variety series.

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

In December 2015, Wayne travelled to Spain to receive the prize “Almeria Tierra de Cine” in Almeria, Andalucia for his long career in the cinema, and in his acceptance speech he noted that his maternal grandparents were born in Madrid and that he is half Spanish.