Born as Mae Kwestel in the Bronx New York City to Simon and Freida Kwestel, she attended Morris High School and studied acting at the American Theatre Wing and with the Theatre Guild. Although she wanted to be an entertainer, her parents, who were Orthodox Jews, actively discouraged her from doing so, at one time forcing her to leave the Theatre Guild school.
Nevertheless, at the age of 17 Questel won a talent contest held at the RKO Fordham Theatre in the Bronx by imitating Helen Kane. She was signed by an agent and began performing in vaudeville as an impressionist. Billed as "Mae Questel - Personality Singer of Personality Songs," she did Fanny Brice, Marlene Dietrich, Eddie Cantor, Mae West, Maurice Chevalier and others, as well as doing animal imitations. She was seen by animator Max Fleischer, who was looking for an actress to provide the voice for his Betty Boop character. Questel's "Boop-boop-a-doop" routine, done in a style similar to the version Helen Kane made popular, while at the same time evoking something of the naughty allure of film star Clara Bow, was exactly what Fleischer wanted, and he hired Questel in 1931. She began as one of a number of actresses providing the character's voice, but soon took over the role exclusively.
From 1931 until 1939, Questel provided the voice of Betty Boop in more than 150 animated shorts, the longest run for any actress doing that voice. During the 1930s she released a recording of "On the Good Ship Lollipop" which sold more than two million copies. In 1988, she reprised the role in a cameo appearance in Who Framed Roger Rabbit.
Along with her voice work, and occasional on-camera appearance in Paramount shorts, Questel also attended Columbia University, where she studied drama.
Beginning in 1933 Questel also provided the voice for Olive Oyl in the Max Fleischer Popeye cartoons beginning with "I Eats Me Spinach" and became essentially the permanent voice until 1938 until her hiatus to start a family. She based Olive's nasal vocal quality and expression, "Oh, dear!" on the character actress ZaSu Pitts and ultimately played the role for 20 years.
Starting in 1938, Margie Hines replaced Mae Questel during the transition to the Miami Studio. Questel returned as the voice of Olive Oyl in 1944 with "The Anvil Chorus Girl" after the studio reorganized as Famous Studios Paramount Pictures had returned to New York. She also filled in for Jack Mercer as the voice of Popeye for a small number of cartoons, made when Mercer was temporarily drawn into war service.
When Hanna-Barbera began making the All New Popeye cartoons for television in 1978, Questel auditioned for the role of Olive Oyl but lost out to Marilyn Schreffler.
In addition to her signature voices of Betty Boop and Olive Oyl, Questel also provided the voice of Little Audrey and Casper, the Friendly Ghost in their respective animated shorts. In the 1950s, she was the voice for the title character of the pioneering interactive Saturday-morning cartoon series Winky Dink and You.
She continued to provide the voices of Betty Boop and Olive Oyl in commercials, television specials and elsewhere until her death. In 1988, she reprised her role as Betty Boop in the film Who Framed Roger Rabbit.
In 1935, Mae Questel played the voice of the Woman in the Shoe in the Max Fleischer cartoon, The Kids in the Shoe.
Questel has played a number of small parts, including appearing with Rudy Vallee as Betty Boop in the 1931 short Musical Justice (1931) and as a nurse in The Musical Doctor in 1932.
In 1961 she was seen as a middle-aged bride in Jerry Lewis' It's Only Money, one of Fanny Brice's mother's card-playing friends at the start of the film Funny Girl in 1968, and as the "Jewish Mama from Hell" in New York Stories in 1989 in Woody Allen's segment titled "Oedipus Wrecks"; she had earlier sung the song "Chameleon Days" on the soundtrack for Allen's film Zelig in 1983. Her last non-voice appearance was as the elderly Aunt Bethany in 1989's National Lampoon's Christmas Vacation.
In 1973, Questel had a role in the short-lived ABC television sitcom The Corner Bar, but she achieved perhaps her greatest visibility in television commercials, notably playing "Aunt Bluebell" in ads for Scott Towels, but also appeared in spots for Playtex, Folger's Coffee and others. She also appeared on panel shows and in daytime soap operas.
Questel had a withered arm; in her on-camera film appearances, she was usually photographed with elbows bent and both hands at her waist or holding an object in the crook of her elbow to make it less obvious that one arm was shorter and smaller than the other.
Questel appeared on Broadway four times:Doctor Social (1948) with Dean Jagger;
Leonard Spigelgass' A Majority of One (1959) with Cedric Hardwicke and Barnard Hughes – she reprised her role (as "Essie Rubin") in the film adaptation;
Enter Laughing (1963) based on the novel by Carl Reiner, with Alan Arkin, Alan Mowbray, Sylvia Sidney and Michael J. Pollard; and
Bajour (1964), the Walter Marks musical, starring Herschel Bernardi, Nancy Dussault and Chita Rivera.
Leo Balkin (married December 22, 1930; the marriage ended in divorce)
Jack E. Shelby (married November 19, 1970; they stayed married up until his death)
Questel died from complications related to Alzheimer's disease at the age of 89 in her Manhattan apartment. She was buried in West Babylon, New York's New Montefiore Cemetery. She had two sons, Robert Balkin, who pre-deceased her, and Richard, who survived her.