John Tyrrell embarked on a show business career at the tender age of 16, partnering with Mack to form the vaudeville dance duo Tyrrell and Mack. The act swiftly gained immense popularity, and for the subsequent decade, they performed at various venues across the country, earning the distinction of being featured players in the renowned revue "George White's Scandals". As the vaudeville era began to decline, Tyrrell astutely recognized the writing on the wall and dedicated himself to honing his acting skills, foreseeing a promising future in the realm of motion pictures.
He spent two years refining his craft with a stock theater company in Connecticut, before venturing to Hollywood, where he was promptly signed to a long-term contract with Columbia Pictures. Tyrrell went on to appear in numerous prestigious films for the studio, primarily in supporting roles. He became a staple in the studio's comedy shorts, frequently sharing the screen with notable comedians such as El Brendel, Andy Clyde, and The Three Stooges, showcasing his versatility by playing a wide range of characters, including con artists, swindlers, and other dubious individuals.