Swayze's film work has included an appearance as a Dancer in the 1980 film Urban Cowboy, as Ruben in the film Father for Charlie, and as Mark in the film Shy People. He also played Col. Sherman Rutherford in a western–noir Hybrid titled Heathens and Thieves in 2012. He also starred in the film Death Ring, and as the Alamo courier James Bonham in Alamo: Price of Freedom, an IMAX film shown in San Antonio, Texas.

Don is an avid skydiver and Cyclist, and races cross country mountain bikes in his spare time. Don was married to the model and Actress Marcia Swayze in December 1985, but they divorced in 1993. Together they had a daughter in 1988, named Danielle. Don is now married to Charlene Swayze.

In 2001, Don was on stage as Pedro in Man of La Mancha, at the Simi Valley Cultural Arts Center. In 2005, he played Roy in the comedy Lone Star at the Beverly Hills Playhouse. In the fall of 2011, he co-starred with Anne Archer in an original stage play titled Jane Fonda: In the Court of Public Opinion, at the Edgemar Theater in Santa Monica, California; he played U.S. Army Sgt. Don Simpson (retired), a wounded veteran of the Vietnam War.

Swayze performed the role of James (Jim) Mackey recently in Season five, episode seven, titled "From This Day Forward", on the Netflix series Longmire. Also currently appearing in two soap operas, The Young and the Restless and Days of Our Lives. In 2010, Swayze guest starred in six episodes in a recurring role as Gus, a werewolf, on the HBO series True Blood. His television drama work includes multiple appearances in Murder She Wrote, The X Files, NYPD Blue, Days of Our Lives, NCIS, Carnivàle, and dozens of other programs. Swayze had a role as a mentally handicapped man suspected of murder in an episode of the television drama Matlock. He played Jesse James in a season-two episode of Lois & Clark: The New Adventures of Superman. He played the demon, Lucius, in an episode of "Charmed" in 2005.He had a recurring role on Criminal Minds, specifically the episodes "The Big Game" and "Revelations", in which he played Charles Hankel, the Father and alternate personality of serial killer Tobias Hankel. On Cold Case, Swayze played the adult Grant Hall. Swayze had a small guest appearance on It's Always Sunny In Philadelphia as a crazy boat captain. He has also appeared on Beyond Belief: Fact or Fiction, and The Bridge. Swayze also appeared in an episode of Sons of Anarchy, season 7. In 2017 he joined the cast of General Hospital for a short stint, in the role of Buzz. Non-speaking part as an abuser and a rapist, called william Dollar in LA Law's 1st series, 1st & 2nd episodes. The rape victim and leukaemia sufferer was Miss Moore played by Alfre Woodard.