In 1912, Sisson applied for work as an extra at Universal Pictures and made her film debut in The Helping Hand (1913).

Sisson received recognition as J. Warren Kerrigan's leading lady in seven successful films, including The Sandhill Lovers (1914), The Oyster Dredger (1915), and A Bogus Bandit (1915).

In 1915, Sisson was offered a contract with Biograph Studios, and the following year she married actor and director Richard Rosson.

Sisson costarred with Harold Lockwood and Virginia Rappe in Paradise Garden (1917), Rudolph Valentino in The Married Virgin (1918), and Constance Talmadge in Experimental Marriage (1919).

On May 1, 1939, Sisson and her husband Rosson, along with two other British nationals, were arrested on a charge of espionage in Vienna, Austria by the Gestapo, allegedly for filming military hardware.