The ventriloquist figures for which he was best known include Jerry Mahoney and Knucklehead Smith. Both figures were carved by Chicago-based figure maker Frank Marshall. His first series as a ventriloquist was actually on radio with Mahoney in 1943; the program was short-lived, as he was overshadowed by Edgar Bergen, though radio historian John Dunning, in his 1998 tome On the Air: The Encyclopedia of Old Time Radio, felt Winchell was the better ventriloquist.

His later career included a great deal of voice-over acting for animated cartoons, notably for Disney and Hanna-Barbera. For the latter, he played the character Dick Dastardly in several series (notably Wacky Races and Dastardly and Muttley), Fleagle Beagle on The Banana Splits Adventure Hour, and Gargamel on The Smurfs. For Disney, he was best known for voicing the character of Tigger from Disney's Winnie the Pooh films, and won a Grammy for his performance in Winnie the Pooh and Tigger Too. Beginning with the television series The New Adventures of Winnie the Pooh, he alternated in the role with Jim Cummings, the current voice of Pooh. In a somewhat controversial move, Cummings took over permanently beginning with The Tigger Movie in 2000 (though Winchell played Tigger one last time in a Walt Disney World Pooh attraction). Other Disney roles included parts in The Aristocats as a Chinese cat and The Fox and the Hound as Boomer the woodpecker. On TV, he played Zummi Gummi on The Gummi Bears, and in commercials, voiced the Scrubbing Bubbles for Dow Chemicals. He also did the voice of Fearless Freddy the Shark Hunter on the Pink Panther cartoon spin-off Misterjaw in 1976.

Other work included on-camera guest appearances on such series as The Beverly Hillbillies, The Lucy Show, and The Brady Bunch, as well as a part in the Jerry Lewis movie Which Way to the Front?. On Love, American Style, he appeared with fellow ventriloquist Shari Lewis in a sketch about two shy people in a waiting room who choose to introduce themselves to each other through their dummies.

Winchell was quite interested in technology - particularly the internet - right up to the time of his death. He created a personal website, www.paulwinchell.com, which he personally developed and maintained until 2004. For a short time he operated the now-defunct website ProtectGod.com, which discussed the theology of the latter years of his life.

He had five children: one son Stacy Paul Winchell and a daughter Stephanie from his first marriage to Dorothy (Dottie) Movitz, a daughter April Winchell, a comedian and voice actress, from his second marriage, to actress Nina Russel, and two step-sons Larry and Keith Freeman from his third marriage, to Jean Freeman.

Winchell's autobiography, Winch (2004), exposed many dark areas of Winchell's life, which had hitherto been kept very private. The autobiography opened old wounds within the Winchell family, prompting daughter April to publicly defend her mother who was negatively portrayed in the book. Winchell estranged his children, who were not immediately notified of his death, as indicated by a message on April's website: "T.T.F.N. I got a phone call a few minutes ago, telling me that my father passed away yesterday. A source close to my dad, or at least, closer than I was, decided to tell me himself, instead of letting me find out on the news, which I appreciate. Apparently a decision had been made not to tell me, or my father's other children. My father was a very troubled and unhappy man. If there is another place after this one, it is my hope that he now has the peace that eluded him on earth."

In a strange coincidence, John Fiedler, who voiced Piglet in the Winnie the Pooh films, died on June 25th - the day after Winchell's death.