She married J. Steven Soles in 1973, when she resided in New York, but then made the move to Los Angeles to work in TV and movies. She and Soles subsequently divorced in 1975, although she decided to retain the name P.J. Soles. She was later married to actor Dennis Quaid from 1978 until their divorce in early 1983. Later that same year, she married Skip Holm, who was a stunt pilot on The Right Stuff (1983). They have a son named Sky (born in 1983) and a daughter named Ashley (born in 1988). She and Holm were divorced in 1998.

Soles moved to Manhattan and began acting in commercials and modeling for fashion magazines, and relocated to Los Angeles in 1975. She was among the hundreds of actors auditioning for Brian De Palma and George Lucas in their joint casting session for Carrie (1976) and Star Wars (1977). She originally auditioned for the role of Princess Leia in Star Wars but the part ultimately went to Carrie Fisher. However, she was cast as Norma Watson in Brian De Palma's Carrie. She starred alongside Sissy Spacek, Nancy Allen, John Travolta, and Piper Laurie. Originally, her character was only supposed to have one line but Palma expanded her role. Soles was injured on the set during filming, when a blast from a fire hose during the prom scene ruptured her eardrum. The same year, she reunited with Carrie costar John Travolta in Randal Kleiser's television film The Boy in the Plastic Bubble. Subsequently, she went to Georgia to film Our Winning Season (1978) and met actor Dennis Quaid. They were married in 1978 in Texas on a dude ranch, and both appeared in the comedy film Breaking Away in 1979.

In 1978, Soles was cast as Lynda van der Klok in John Carpenter's Halloween (1978), the final victim of the Michael Myers character in the classic horror film. John Carpenter wanted her for his film Halloween after seeing Carrie. He wrote the part of Lynda especially for her because of the way she said the word "totally". Soles starred in Rock 'n' Roll High School (1979) with The Ramones and was injured during filming. She has a singing credit for a second version of the title song on the movie's Soundtrack. She reprised the role of Riff Randell in the artwork for the Local H album Whatever Happened to P.J. Soles?. In 1980, Soles portrayed Private Wanda Winter in the comedy film Private Benjamin. The following year, she portrayed Bill Murray's girlfriend, Stella Hansen, in the comedy film Stripes.

In 1985, Soles starred alongside Jessica Lange as Wanda in Karel Reisz's biographical film Sweet Dreams. In 1999, Soles was cast in the black comedy film Jawbreaker. In 2005, Soles played the victim, Susan, of a family on a murderous rampage in the Rob Zombie movie The Devil's Rejects. In 2012, she starred alongside Barbara Steele, Heather Langenkamp, Camille Keaton, and Adrienne King in The Butterfly Room.