Here's a couple of possibilities:

Patty Duke Show - Paul O'Keefe
Diff'rent Strokes - Todd Bridges

Barbara Eden - I Dream of Jeannie

Barbara Eden - I Dream of Jeannie

Barbara Eden is also the sole survivor of the 1950's sitcom How to Marry a Millionaire, as her castmates Merry Anders, Lori Nelson (season 1) and Lisa Gaye (season 2) have all passed away.

Tina Louise - Gilligan’s Island
Betty White - The Golden Girls
Adrienne Barbeau - Maude

Jay North Dennis the Menace

Ron Howard The Andy Griffith Show

Erin Murphy - Bewitched
Ed Asner - Mary Tyler Moore Show

Dick van Dyke-DICK VAN DYKE

Clint Eastwood - Rawhide
Yoshio Yoda (Fuji) - McHale's Navy
Larry Storch - F Troop

Michael Douglas, The Streets of San Francisco

Demond Wilson

https://ic-cdn.flipboard.com/popculture.com/4d8fea3604e70b2eb79883e6fb19403479494eea/_medium.webp

Joyce Randolph is the only living cast member from The Honeymooners and Tina Louise is the only surviving cast member from Gilligan's Island

Joyce Randolph is the only living cast member from The Honeymooners and Tina Louise is the only surviving cast member from Gilligan's Island

I think the thread title should be changed to lead/cast member. Some of the ones mentioned so far were definitely not leads.

Max Baer,Jr. is the only surviving cast member of ' The Beverly Hillbillies' (and since his name was in the 'moving car opening credits', I'd say he was one of the four 'leads').

With Donna Douglas's death in 2015, he said he was the last survivor (including crew) and I'm not how many guest performers are still living.