Born in 1914 in Morenci in Arizona, in 1917 his family moved to Los Angeles where Perez later attended high school. An athlete, he took part in football, baseball and track. Two years after graduating he was hired by Leon Schlesinger as a trainee animator. On 17 April 1938 he married Connie (née Perez).
'Manny' Perez worked on over 300 cartoons during the 'Golden Age of American Animation', mainly for Warner Bros. Cartoons, for whom he started animating in 1938, but also for Bill Melendez Productions, DePatie-Freleng Enterprises and Hanna-Barbera. His first credited cartoon was Porky's Bear Facts (1941). Among the cartoons he animated were those featuring Bugs Bunny, Daffy Duck, Porky Pig, Tweetie and Sylvester, Quick Draw McGraw, the Pink Panther, Charlie Brown, Wile E. Coyote and The Road Runner, Doctor Dolittle, The Cat in the Hat, Fritz the Cat and Plastic Man, among many others.
A member of the labor union The Screen Cartoonists Guild, Perez was one of the animators involved in the 'Looney Tunes Lock Out' of 1941, when Leon Schlesinger, who had been producing cartoons for Warner Bros. Cartoons since the mid-1930s, locked out those animators who had joined the Guild, including Perez. After six days Schlesinger relented and allowed them to go back to work.
Despite having worked for Friz Freleng for about ten years, the two did not get along. According to animator Greg Duffell in 1999:
Virgil Ross told me that Perez was "Friz's whipping boy"... Virgil felt that Friz belittled Manny, then when Manny left Virgil felt that he became the target of Friz’ wrath... I met Manny Perez in 1975 at San Rio Productions during the production of a feature film (I've forgotten the title now) that was like a rock music Fantasia. I was quite thrilled, of course, to meet Mr. Perez (didn't know he'd be there) and started to ask him questions about his work. At that time, I wasn't clear which animator did what, though I could see the various styles while watching the cartoons. Manny was very elusive about identifying any of his work for me. At the mention of Friz' name he said these words, with a tense smile, that I'll never forget: "You know, I worked so long for him....well...I got to hate that little guy..."
In his later years Perez worked on Journey Back to Oz (1971); the animated version of The Lord of the Rings (1978), and The Plastic Man Comedy/Adventure Show (1979).
He died in January 1981 aged 66 at Van Nuys in California.