Mercer began his work in cartoons as an "inbetweener", an apprentice animator at Fleischer Studios. As noted in an interviewer from ca. 1975, captured in the specials for Popeye the Sailor: 1938-1940, Volume 2, Mercer liked to imitate voices, including one close call where he mimicked the high-pitched and loud voice of one of the Fleischer's wives after he mistakenly thought she had left the studio.
When Billy Costello, the original cartoon voice of Popeye (1933-35), became difficult to work with, he was dismissed. Mercer had begun imitating Costello's interpretation of Popeye, and practiced it until his voiced "cracked" just right and he had it down. Searching for a replacement for Costello, Lou Fleischer heard Mercer singing the Popeye song and gave him the job of doing the Popeye voice. Mercer's first cartoon was "King of the Mardi Gras" (1935).
Mercer continued to voice the one-eyed sailor for the Fleischers, for Paramount's Famous Studios cartoons (1942-57), for a series of television cartoons for King Features Syndicate, and for a Saturday morning cartoon show (1978), produced by William Hanna and Joseph Barbera. Mercer also did other cartoon voices, including all the voices for a series of Felix the Cat cartoons produced in 1959-60. Mercer also did the voices of Wimpy, Poopdeck Pappy, Popeye's nephews, King Little in Fleischer's Gulliver's Travels (1939), and a number of voices for Fleischer's Mister Bug Goes to Town (1941). Mercer's own natural voice is relatively high-pitched for a man, and he was able to do some of the female voices as well.
Originally a resident of New York City, Mercer moved to Miami, Florida when Fleischer Studios relocated there. When Famous Studios took over the Popeye cartoons, Mercer moved back to New York. In the late 1970s he lived briefly in Los Angeles, but moved to Queens, New York, where he died in 1984. After his death, Maurice LaMarche took over the role of Popeye.
Mercer's first wife was Margie Hines, who provided the voice of Olive Oyl from 1939 to 1944.