Jenkins was born and raised in DeKalb, a university town in Illinois. His mother, Mary Elizabeth (née Wheeler), was a housewife, and his father, Dale Steven Jenkins, was a dentist. Before he was an actor, Jenkins drove a linen truck (his boss was actor John C. Reilly's father). Jenkins earned a degree in drama from Illinois Wesleyan University before relocating to Rhode Island. While attending Illinois Wesleyan, Jenkins was a member of Phi Gamma Delta.

He worked as an actor with the Trinity Repertory Company in Providence, Rhode Island while breaking into film with a bit part in Feasting with Panthers (1974), a television movie, and continued as a celebrated member of Trinity's resident acting company and served as Artistic Director of the theatre from 1990-4.

Since his film debut in the television movie Feasting with Panthers (1974), he has steadily been working in film and television. Some of his earlier film credits include Hannah and Her Sisters (1986), The Witches of Eastwick (1987), How to Make an American Quilt (1995), Snow Falling On Cedars (1999), North Country (2005). He is also an occasional collaborator with the director siblings the Farrelly brothers, who have worked with Jenkins in There's Something About Mary (1998), Me, Myself, & Irene (2000), Outside Providence (1999), and Say It Isn't So (2001). He has also worked frequently with the Coen Brothers: The Man Who Wasn't There (2001), Intolerable Cruelty (2003), and Burn After Reading (2008). Although known primarily for supporting parts, he had a critically acclaimed lead role in The Visitor (2008), for which he was nominated for the Independent Spirit Award for Best Lead Male and a nomination for an Academy Award for Best Actor. Jenkins won the International Press Academy's Satellite Award for Best Actor - Motion Picture Drama.

Jenkins has been cast in the Joss Whedon/Drew Goddard horror The Cabin in the Woods (2010).

Jenkins is perhaps best known for playing Nathaniel Fisher in the HBO drama series Six Feet Under. His character is a deceased patriarch of the Fisher family, who regularly appears to his family as a ghost or in a dream. He played the role since the show began in 2001, through to its final season in 2005. He and his castmates received their Screen Actors Guild Award nomination for Outstanding Performance by an Ensemble in a Drama Series in 2002.

He married Sharon Rayna Friedrick on August 23, 1969 and together they have two children, Sarah Pamela and Andrew Dale. He currently resides in Cumberland, Rhode Island.