Born to Italian immigrants in New York City, Barbera joined Van Beuren Studios in 1927 and subsequently Terrytoons in 1936.

[6]: 17–18, 19, 34, 58, 61, 128, 208 [7][5][a][9][10][11][12][excessive citations] He grew up speaking Italian, He had two brothers, Larry (1909–1982) and Ted (1919–1994), both of whom served in World War II.

Ted was a fighter pilot with the United States Army Air Forces and served in the Aleutian Islands Campaign.

They had four children: two sons, Neal and an infant boy who died two days after his birth, and two daughters, Lynn and Jayne, who has been a producer in her own right.

[6]: 58, 61, 66, 90, 129  Shortly after his divorce, Barbera met his second wife, Sheila Holden, sister of British rock and roll singer Vince Taylor, at Musso & Frank's restaurant, where she worked as bookkeeper and cashier.

Unlike Dorothy, who preferred to stay at home with the children, Sheila enjoyed the Hollywood social scene that Barbera often frequented.

[18][19] Lured by a substantial salary increase, Barbera left Terrytoons and New York for the new Metro-Goldwyn-Mayer cartoon studio in California in 1937.

[21][22] Barbera and Hanna worked alongside animator Tex Avery, who had created Daffy Duck and co-created Bugs Bunny for Warner Bros. and directed Droopy cartoons at MGM.

[20]: 33 [23]: 18 In 1940, Hanna and Barbera jointly directed Puss Gets the Boot, which was nominated for an Academy Award for Best (Cartoon) Short Subject.

[6]: 75–76  Surprised by the success of Puss Gets the Boot, Barbera and Hanna ignored Quimby's resistance[20]: 45  and continued developing the cat-and-mouse theme.

Barbera and Hanna met with Quimby, who discovered that although Ising had taken sole credit for producing Puss Gets the Boot, he never worked on it.

Quimby, who wanted to start a new animation unit independent from Ising, then permitted Hanna and Barbera to pursue their cat-and-mouse idea.

[6]: 78–79 Modeled after the Puss Gets the Boot characters with slight differences, the series followed Jerry, the pesky rodent who continuously outwitted his feline foe, Tom.

[21][33] Tom and Jerry also made guest appearances in several of MGM's live-action films, including Anchors Aweigh (1945) and, Invitation to the Dance (1956) with Gene Kelly, and Dangerous When Wet (1953) with Esther Williams.

[33][34][35] In addition to his work in animated cartoons, Barbera and Tom and Jerry layout artist Harvey Eisenberg moonlit to run a comic book company named Dearfield Publishing.

[6]: 120 [17][20]: 77, 146  A coin toss gave Hanna precedence in the naming of the new company [20]: Foreword  first called H-B Enterprises but soon changed to Hanna-Barbera Productions.

[17][40] Barbera and Hanna's MGM colleague George Sidney, the director of Anchors Aweigh, became the third partner and business manager in the company and arranged a deal for distribution and working capital with Screen Gems, the television division of Columbia Pictures, who took part ownership of the new studio.

[35][42] A parody of The Honeymooners, the new show followed a typical Stone Age family with home appliances, talking animals, and celebrity guests.

[35][41][43] Fred Flintstone's signature exclamation, "yabba dabba doo," soon entered everyday usage,[8][35] and the show boosted the studio to the top of the TV cartoon field.

[27][33][44] The company also produced animated specials based on Alice in Wonderland, Jack and the Beanstalk, Cyrano de Bergerac, and feature-length films Charlotte's Web and Heidi's Song.

[22][45] The number of drawings for a seven-minute cartoon decreased from 14,000 to nearly 2,000, and the company implemented innovative techniques such as rapid background changes to improve viewing.

[46]: 75 [47]: 54  The new style did not limit the success of their animated shows, enabling Hanna-Barbera to stay in business, providing employment to many who would otherwise have been out of work.

[45][49] In December 1966, Hanna-Barbera Productions was sold to Taft Broadcasting, renamed Great American Communications in 1987, for $12 million.

Barbera remained active as an executive producer for Warner Bros. on direct-to-video cartoon features and television series such as What's New, Scooby-Doo?

[59] On December 18, 2006, Barbera died of natural causes at his home in Studio City, Los Angeles, California, at 95, ending a seventy-year career in animation.

[60] His wife Sheila was at his side at the end;[60] he was also survived by three children from his first marriage: Jayne (who worked for Hanna-Barbera), Lynn, and Neal.

Most of the cartoons Barbera and Hanna created revolved around close friendship or partnership; this theme is evident with Fred and Barney, Wilma Flintstone and Betty Rubble, Dick Dastardly and Muttley, Tom and Jerry, Scooby and Shaggy, Ruff and Reddy, Jake Clawson/Razor and Chance Furlong/T-Bone, The Jetson family and Yogi & Boo-Boo.

[48][61] Leonard Maltin says the Hanna–Barbera team "held a record for producing consistently superior cartoons using the same characters year after year—without a break or change in routine.

Animation dedicated a wall sculpture at the Television Academy's Hall of Fame Plaza in North Hollywood to Hanna and Barbera.

Jackson autographed a picture of himself and his niece Nicole for Barbera with the words: "To my hero of yesterday, today, and tomorrow, with many thanks for all the many cartoon friends you gave me as a child.