After serving in the military during World War I, Chandler pursued higher education at the University of Illinois, where he financed his studies by showcasing his exceptional jazz violin skills in a band. Following his academic endeavors, he returned to the vaudeville circuit in the early 1920s, eventually transitioning into the film industry in 1928.
During the early stages of his cinematic career, Chandler primarily focused on creating short, one- and two-reel comedies, with arguably his most notable achievement being the 1933 film "The Fatal Glass of Beer," which co-starred the renowned W.C. Fields. Although he was often cast in comedic roles, Chandler demonstrated his versatility by taking on more substantial assignments, such as portraying the simple-minded husband of Ginger Rogers, Amos, in the 1942 film "Roxie Hart."
George Chandler was fortunate to have had the guidance of director William A. Wellman, who utilized his talents in over twenty of his films. On television, Chandler left a lasting impression as the lovable and memorable Uncle Petrie in the popular series "Lassie" in 1954. He also made numerous guest appearances in various TV shows, with one of his most enjoyable roles being that of the elderly man who sells a haunted Model A to a dubious second-hand car dealer, Jack Carson, with intriguing consequences, in the 1959 episode "The Whole Truth" of "The Twilight Zone." Prior to replacing Ronald Reagan as the president of the Screen Actors Guild, Chandler had served as treasurer for twelve years, from 1948 to 1960.