Treat Williams was thrown from his motorbike in Vermont on Monday after being hit by an SUV turning left, police said.
He was airlifted to hospital with critical injuries, but pronounced dead on arrival.
The actor recorded over 130 screen credits in a career that spanned almost 50 years.
“As you can imagine, we are shocked and greatly bereaved at this time,” a family statement published by Variety magazine said.
“Treat was full of love for his family, for his life and for his craft, and was truly at the top of his game in all of it.”
Williams’ agent of 15 years, Barry McPherson, described him as “the nicest guy” who was “so talented.”
“He was an actor’s actor,” McPherson told People magazine, adding that Williams had been at “the heart of Hollywood since the late 1970s.”
Actor Wendell Pierce described Williams on social media as a “passionate… creative man” whose “adventurous spirit was infectious.”
Following his 1979 breakthrough in Hair as hippie George Berger, Williams appeared in Steven Spielberg’s (1979), Once Upon A Time In America (1984), Dead Heat (1988), Things to Do in Denver When You’re Dead (1995) and Deep Rising (1998).
He was also known for his stage acting, with roles in Stephen Sondheim’s Follies and as Danny Zuko in the original Broadway production of Grease.
In the early 2000s, Williams appeared as widowed Dr Andy Brown in four series of the US TV drama Everwood, and he also took on roles in Chesapeake Shores, Blue Bloods and Chicago Fire.
Born Richard Treat Williams in Connecticut in 1951, he is survived by his wife Pam Van Sant, whom he married in 1988. The couple had two children.