Selby was born on February 5, 1941, in Morgantown, West Virginia, the son of Sarah E. (née McIntyre) and Clyde Ira Selby, a carpenter. He attended West Virginia University in his hometown, earning Bachelor of Science and Master's degrees in theater, followed by a Ph.D. from Southern Illinois University.
Midway through his career at WVU, David joined the cast of "Honey in the Rock", a new civil war drama at Grandview State Park near Beckley, West Virginia, where he portrayed the Rev. Gordon Battelle, a Methodist minister who advocated for separation from Virginia. He brought his Dark Shadows character to film with the second Dark Shadows film, Night of Dark Shadows, released in 1971, after the TV series' cancellation. In 1973 he played Roger Castle in the 1977 miniseries Washington: Behind Closed Doors. In 1979, Selby also turned down the role of Gary Ewing on Knots Landing, hence, the role was ultimately given to Ted Shackelford who then initially portrayed the role on Dallas. In 1981, Selby played the villainous Michael Tyrone on the final season of the NBC primetime serial Flamingo Road. Immediately after its cancellation in 1982, Selby joined the cast of Falcon Crest as Richard Channing. When Richard was originally written into Falcon Crest, he was considered an antagonist. However, over the years the character became more of a protagonist and by the final season he was the central character of the show in the absence of the show's main star Jane Wyman, all because of her health problems.
Selby's film credits include Up the Sandbox (1972) with Barbra Streisand, U-Turn (1973), The Super Cops (1974), Rich Kids (1979), Raise the Titanic (1980), Rich and Famous (1981), Intersection (1994), White Squall (1996), D3: The Mighty Ducks (1996) and Surviving Christmas (2004). In 2010, he appeared in The Social Network as the attorney representing the Winklevoss brothers. He reprised the role of Quentin Collins for a new series of Dark Shadows audio dramas from Big Finish Productions.
On the 200th anniversary of Abraham Lincoln's birthday, Selby appeared onstage with Barack Obama and portrayed Lincoln in a scene from the play The Heavens are Hung in Black at the historic reopening of Ford's Theatre. He played Abraham Lincoln again in the Touched by an Angel episode "Beautiful Dreamer".
He appeared in the Mad Men season 3 episode, "The Arrangements", and in the film Equals.
In 2012, he co-starred in Batman: The Dark Knight Returns, a two-part direct-to-video animated film adaptation of the 1986 graphic novel The Dark Knight Returns, portraying Commissioner James Gordon.
In 2017, Selby had a recurring role in FX's Marvel Comics X-Men drama, Legion.
His writing includes the plays Lincoln and James and Final Assault as well as the poetry collections My Mother's Autumn and Happenstance. His novels are Lincoln's Better Angel and The Blue Door. A Better Place combines memoir and social commentary to discuss Selby's West Virginia upbringing. In 2010, Selby published My Shadowed Past, chronicling what it was like to work on Dark Shadows during the turbulent late 1960s and early 1970s.1971: Night of Dark Shadows
1972: Up the Sandbox
1974: The Super Cops
1979: Rich Kids
1980: Raise the Titanic
1981: Rich and Famous
1991: Dying Young
1992: Grave Secrets: The Legacy of Hilltop Drive
1996: White Squall
1996: Headless Body in Topless Bar
1996: D3: The Mighty Ducks
2004: Surviving Christmas
2006: End Game
2010: The Social Network
2013: Are You Here
West Virginia University in 1998 awarded Selby its first Life Achievement Award from the College of Creative Arts, and an honorary doctorate in 2004.