Keach first distinguished himself in Off-Broadway productions and remains a prominent figure in American theatre across his career, particularly as a noted Shakespearean.

[4] His other notable film credits include Brewster McCloud (1970), Doc (1971), The Life and Times of Judge Roy Bean (1972), Luther (1973), Slave of the Cannibal God (1979), The Ninth Configuration (1980), The Long Riders (1980), Roadgames (1981), Batman: Mask of the Phantasm (1992), Escape from L.A. (1996), American History X (1998), The Bourne Legacy (2012) and Nebraska (2013).

[9] Keach played the title role in MacBird!, an Off-Broadway anti-war satire by Barbara Garson staged at the Village Gate in 1966.

He played the lead actor in The Nude Paper Sermon, an avant-garde musical theatre piece for media presentation, commissioned by Nonesuch Records by composer Eric Salzman.

In the early 1980s, he starred in the title role of the national touring company of the musical Barnum, composed by Cy Coleman.

[12] In 1991 and 1996 he won Helen Hayes Awards for Outstanding Actor for his work in Richard III and Macbeth with the Shakespeare Theatre Company.

In the summer of 2009, Shakespeare Theatre Company remounted the production of King Lear at Sidney Harman Hall in Washington, D.C., for which Keach won another Helen Hayes Award for Outstanding Actor.

[13] On December 16, 2010, Keach began performances as patriarch Lyman Wyeth in the off-Broadway premiere of Jon Robin Baitz' acclaimed new play Other Desert Cities.

[18] On June 2, the Goodman Theatre announced that the entire run would be canceled after Keach's doctors advised a period of rest and recuperation.

He went on to play Kane in the 1980 movie The Ninth Configuration, written and directed by Exorcist author William Peter Blatty; this role was itself intended for Nicol Williamson.

Keach was narrator of the 1973 Formula One racing documentary Champions Forever, The Quick and the Dead by Claude du Boc.

In 1978, he played a role of explorer and scientist in Slave of the Cannibal God, co-starring former Bond girl Ursula Andress.

In Oliver Stone's 2008 biographical film W., Keach portrays a Texas preacher whose spiritual guidance begins with George W. Bush's AA experience, but extends long thereafter.

Keach's first-ever experience as a series regular on a television program was playing the lead role of Lieutenant Ben Logan in Caribe in 1975.

[22] He played Barabbas in 1977's Jesus of Nazareth, and portrayed Jonas Steele, a psychic and Scout of the United States Army in the 1982 CBS miniseries, The Blue and the Gray.

Cast members of Titus have commented they enjoyed working with Keach because he would find a way to make even the driest line funny.

[24] Keach lent his voice to The Simpsons episodes "Hungry, Hungry Homer", "Old Yeller-Belly", "Marge and Homer Turn a Couple Play", and "Waiting for Duffman", portraying Duff Brewery President Howard K. Duff VIII, and the Batman Beyond episode "Lost Soul" as Robert Vance, a deceased businessman resurrected as an artificial intelligence.

He also guest starred in a 2005 episode of the sitcom Will & Grace, and had a recurring role as Warden Henry Pope in the Fox drama Prison Break.

It was directed by Kevin Connor, and starred Angus Macfadyen, with Richard Chamberlain, David Winters, and Jessica Chastain.

[25] In 2011, Keach co-starred as "Pops", the father of the main character in the short lived boxing drama series Lights Out.

He played the role of Robert Vesco, Raymond Reddington's former mentor and criminal muse, on the TV series The Blacklist.

From 1989 to 1992, he was host of the syndicated informational reenactment show, Missing Reward, which had a similar format to the popular Unsolved Mysteries at the time.

[citation needed] In 2008, Keach once again reprised his famous role as Mike Hammer in a series of full-cast radio dramatizations for Blackstone Audio.

[28] He also voiced both Job and Paul the Apostle in The Word of Promise, a 2007 dramatic audio presentation based on the New King James Version.