Pernell Williams Bonanza
Valerie Harper Valerie, only because she was fired
George Clooney ER
Julianna Margulies ER
Joe Marie Payton Family Matters
Jon Amos Good Times because he was fired
Esther Roll Good Times but then she came back.
Shelly Long Cheers
Charlie Sheen 2 and Half Men because he was fired.
Ron Howard Happy Days
Cindy Williams Lavern and Shirley
Topher Grace That's 70's Show

Harvey Korman left the Carol Burnett Show after season 10.
Ivan Dixon left Hogan's Heroes after season 5.
Gary Burghoff left M*A*S*H after season 8.
Steven Kampmann left Newhart after season 2.
Sid Melton left Green Acres after season 5.
Richard Thomas left The Waltons after season 6.

Steve Carell left "The Office" after season seven (of nine).
Khandi Alexander left "NewsRadio" early in season four (of five).
Michael J. Fox left "Spin City" after season four (of six).
Arye Gross left "Ellen" early in season three (of five).
Chevy Chase left "Community" after season four (of six).
Donald Glover left "Community" early in season five (of six).
Yvette Nicole Brown left "Community" after season five (of six).
Don Knotts left "The Andy Griffith Show" after season five (of six).
Dick York left "Bewitched" after season five (of eight).
Bitty Schram left "Monk" mid season three (of eight).
Thomas Haden Church left "Wings" after season six (of eight).

There are plenty more but I'll some for others, haha.

McLean Stevenson - M*A*S*H
Wayne Rogers - M*A*S*H
Larry Linville - M*A*S*H
Donny Most - Happy Days
Pat Morita - Happy Days

James MacArthur, Hawaii Five-O (left after 11 seasons)
Gregory Sierra, Barney Miller (left after 2 seasons)

Pernell Roberts left "Bonanza" after or at the end of season 6 (of fourteen).

Don Grady (Robbie Douglas) left My Three Sons.
Tim Considine (Mike Douglas) left My Three Sons.

William Frawley of My Three Sons when he became ill.
Cindy Williams-Laverne and Shirley

Suzanne Somers was fired off Three's Company in the beginning of season 5 (of 8)
Larry Wilcox left CHiPs after season 5 (of 6)

Charlotte Rae left The Facts of Life.
Robert Guillaume left SOAP.

Michael Learned (Olivia) left The Waltons after season 8.
Ed Ames (Mingo) left Daniel Boone after season 4.

Janet Hubert was removed from The Fresh Prince of Bel Air. :(

Stars whose careers tanked after leaving hit shows (Stars whose careers tanked after leaving hit shows Read More: http://www.looper.com/11431/stars-whose-careers-tanked-leaving-hit-shows/?utm_campaign=clip)

Zach Braff (Scrubs)
David Caruso (NYPD Blue)
Polly Holliday (Alice)
Denise Crosby (Star Trek: The Next Generation) Left only about halfway through the first season because she actually wasn't happy in the role of Security Chief Tasha Yar. She later guest starred in several episodes of TNG in a bizarre twist as Tasha Yar's half human-half Romulan adult daughter Sela.

Ed.

Stacy Ferguson (Kids Incorporated)
Andre Braugher (Homicide: Life on the Street)
Jerry Orbach (Law & Order)
Johnny Depp (21 Jump Street)
Jason Priestley (Beverly Hills, 90210)
Harry Hamlin (L.A. Law)
Ed Flanders (St. Elsewhere)
Ed Marinaro (Hill Street Blues)
Howard Rollins (In the Heat of the Night)
Lisa Bonet (The Cosby Show, A Different World)
Stepfanie Kramer (Hunter)
Charlotte Rae (Diff'rent Strokes, The Facts of Life)
Jackee Harry (227)
John Diehl (Miami Vice)
William Petersen (CSI: Crime Scene Investigation)
Olivia d'Abo (The Wonder Years)

Victoria Principal, original-recipe Dallas, after 10 seasons