Born in Philadelphia, Pennsylvania, into a family of vaudeville performers, Quillan made his stage debut at the age of seven alongside his parents, Scottish-born Joseph Quillan and his wife Sarah, as well as his siblings in their act titled 'The Rising Generation'. By the early 1920s he was called upon by film Director Mack Sennett to perform a screen test for Mack Sennett Studios. Sennett signed Quillan to a contract in 1922.

Quillan's very first film appearance was in the 1922 comedy short Up and at 'Em. His next performance was in the 1926 comedy short The Love Sundae opposite Actress Alice Day. His next ten film appearances (all released in 1926) were all comedy shorts that were vehicles for Day. He would spend most of the remaining years of the 1920s in comedy shorts featuring actresses Ruth Taylor and Madeline Hurlock. In 1928, Quillan starred in the comedy A Little Bit of Everything, notable because it featured his siblings Marie, Joseph and John in starring roles. Marie Quillan would eventually embark on a film career of her own and appear opposite her brother once more, in the 1929 comedy Nosy Neighbors.

Quillan's first feature-length film was the 1928 comedy-drama Show Folks opposite Actress Lina Basquette, in which Quillan appropriately plays a vaudeville Dancer. The film was a modest success and also featured Actress Carole Lombard. Quillan's breakout role (and first dramatic film role) was in the 1929 Cecil B. DeMille directed The Godless Girl. The film paired Quillan once again with Basquette and starred Marie Prevost and Noah Beery, Sr. His subsequent exposure from the film landed him a contract with Pathé studios.

Quillan would remain a popular leading and secondary actor throughout the sound film era and would appear in such notable films as 1935's Mutiny on the Bounty with Clark Gable, Charles Laughton, and Franchot Tone, 1939's Young Mr. Lincoln opposite Henry Fonda and Alice Brady, as 'Connie Rivers' in John Ford's 1940 film adaptation of the John Steinbeck novel The Grapes of Wrath opposite Henry Fonda, in 1943's Alaska Highway and It Ain't Hay opposite the comedic duo Abbott and Costello.

Quillan's breezy screen personality was seen in "B" musicals, comedies, and even serials during the 1940s. In 1948 Columbia Pictures Producer Jules White teamed Quillan with veteran movie comic Wally Vernon for a series of comedy short subjects. White emphasized extreme physical comedy in these films, and Vernon and Quillan made a good team, enthusiastically engaging in pratfalling, kick-in-the-pants slapstick. The series ran through 1956.

Through the 1950s and 1960s, Quillan continued to appear in motion pictures, but in increasingly smaller roles and often in bit parts. One notable appearance of the era was his role of 'Sandy' in the 1954 Vincente Minnelli directed musical Brigadoon, starring Gene Kelly, Van Johnson and Cyd Charisse. Quillan also appeared in the uncredited role of 'Mr.Cassidy' in the 1969 Gene Kelly film adaptation of Hello, Dolly!, starring Barbra Streisand and Walter Matthau and featuring Louis Armstrong. Quillan appeared in My Three Sons as Mr Hewlett (1961) and also appeared on the western television adventure series The Rifleman as Angus Evans. He appeared twice in the fourth season: in “Mark's Rifle” (episode 150) and “Conflict” (episode 155).

In the 1970s, Quillan made guest appearances on such varied television series as Mannix, Here's Lucy, Chico and the Man and Baretta. After meeting and befriending actor and Director Michael Landon, he played numerous bit roles in the popular television series Little House on the Prairie. Quillan also performed in the Landon-directed series Highway to Heaven and Father Murphy during the 1980s. Quillan made his last television appearance in a 1987 episode of the television crime-mystery series Matlock.

Quillan died of cancer in Burbank, California in 1990 and was interred at the San Fernando Mission Cemetery in Mission Hills, Los Angeles, California.