Ryan was born on January 11, 1928, in Cincinnati, Ohio, and raised in Louisville, Kentucky. His father was a novelty salesman. He served in the United States Navy during the Korean War. After the Korean War, he went to the Barter Theatre in Abingdon, Virginia. There, he went on to make his acting debut in Thunder Road along with the theatre's founder Robert Porterfield.

Ryan was an original cast member on the cult TV soap opera Dark Shadows, playing Burke Devlin until he was fired from the show in June 1967 due to his alcoholism, and replaced by Anthony George.

He appeared in an episode of Cannon, "Fool's Gold" in 1971, and in ABC's The Streets of San Francisco episode "The Unicorn". In 1973, he played the lead in the NBC adventure show Chase, with co-stars Wayne Maunder and Reid Smith.

Ryan married, secondly, to Lynda Morse from 1972 until they divorced; the couple had three children.

In 1976-77, he portrayed the leading character on Executive Suite and worked with his Future on-screen wife from Dharma & Greg, Susan Sullivan, in the short-lived series Julie Farr, M.D..

In 1980, Ryan played wagon master Cooper Hawkins in the CBS Western miniseries The Chisholms, taking a wagon train of pioneers to California during the 1840s, and becoming the de facto head of the Chisholm family after the death of patriarch Hadley Chisholm.

His other acting credits include Liar, Liar, Cannon, Magnum Force playing as Dirty Harry's ill-fated despondent best friend and fellow police officer, a burned out motorcycle patrolman named Charlie McCoy, Lethal Weapon playing the key villain, General Peter McAllister, Grosse Pointe Blank, Electra Glide in Blue, and Hot Shots! Part Deux playing senator Grey Edwards. And in 1985, he portrayed Tillet Main, the patriarch of the Main family in the first North and South miniseries.

Ryan appeared in NBC's The A-Team episode "Waste 'Em", as Grant Everett in the two-part Silk Stalkings episode "Partners", and as Kyle Riker, the father of Commander william Riker, in the Star Trek: The Next Generation episode "The Icarus Factor"; Ryan had earlier been considered for the part of series lead Captain Jean-Luc Picard. He also portrayed the roles of the abusive boyfriend of Blanche Deveraux in The Golden Girls and a police officer in a 1993 episode of NYPD Blue. That same year, Ryan was Dallas Shields in Renegade. In 1994, he appeared in the television movie, Hart to Hart: Home Is Where the Hart Is, and in 1995, he appeared in Judge Dredd and Halloween: The Curse of Michael Myers.

He played the role of Greg's father Edward Montgomery on the show Dharma & Greg, which ran from 1997 to 2002. The following year, Ryan voiced Highfather on Justice League.