Schlesinger was born in Philadelphia. After working at a theater as an usher, songbook agent, actor, and manager, he became the head of Pacific Art and Title, where most of his business was producing title cards for silent films. As talking pictures ("talkies") gained popularity in 1929 and 1930, Schlesinger looked for ways to cash in and stay in business. Legend claims that he helped finance the Warner brothers' first talkie, The Jazz Singer. He then secured a contract with the studio to produce its brand-new Looney Tunes series, and he signed animators Hugh Harman and Rudy Ising to create these cartoons with their Bosko character as the star.
Schlesinger was a shrewd businessman with a keen eye for talent. When Harman and Ising left Warner Bros. with Bosko in 1934, Schlesinger set up his own studio on the Warner Bros. lot on Sunset Boulevard. He wooed animators away from other studios, including some of those who had departed with Harmon and Ising. One of these was Friz Freleng, who Schlesinger promoted to take over production of Looney Tunes and to develop the sister series, Merrie Melodies. Freleng's talent quickly shone through, and Schlesinger's hiring of Frederick "Tex" Avery, Carl Stalling, and Frank Tashlin further increased the quality of the studio's output. He later added Bob Clampett, Chuck Jones, and Mel Blanc to the staff, and collectively, these men would create such famous characters as Porky Pig, Daffy Duck, and Bugs Bunny. Schlesinger largely took a "hands off" approach to the animation unit, allowing his directors unbridled freedom to create what they wished. The films just had to do well in the theaters.
Schlesinger's hard-nosed business practices cannot be overstated. His animators worked in the dilapidated "Termite Terrace", and Schlesinger briefly shut down the studio in 1941 and 1942 when unionized employees demanded a pay raise. On another occasion, he boycotted the Academy Awards for what he claimed was preferential treatment for Walt Disney Studios. He also farmed some of the Looney Tunes out to his brother-in-law, Ray Katz, for the tax breaks. Schlesinger was also known (among his animators, at least) for his lisp. In fact, Mel Blanc patterned the voices of both Daffy Duck and Sylvester the cat on Schlesinger, something the producer never acknowledged noticing. Animators who worked with him also found him conceited and somewhat foppish, wearing too much cologne and dressing like a dandy, cane and all.
Schlesinger remained head of the animation studio until 1944 when he sold his assets to Warner Bros. He continued to market the characters until his death in 1949. Schlesinger also produced a number of B-movie Westerns in the 1930s.