In July 1893, 17-year-old Cissy Loftus made her début at the Oxford Music Hall in London, followed by an appearance at the Palace Theatre of Varieties.

[5] With the Rehan troupe she played Washington, DC, St. Louis, Missouri, and Chicago, Illinois as "Miss Cecile" in a playbill.

Some of the productions she appeared in are The Man of Forty (1900), If I Were King (1901) by her husband Justin Huntly McCarthy, Hamlet (1903) with E.H. Sothern, the Victor Herbert operetta Dream City (1906), Venus (1927) with Tyrone Power, Sr., Three-Cornered Moon (1933) with Ruth Gordon, Clare Boothe Luce's Abide With Me (1935), and Little Dark Horse (1941).

As Cissie Loftus, she wrote lyrics and music for songs in a number of productions, including The Belle of Bridgeport (1900)[9] and The Lancers (1907).

Loftus also appeared in cinema from the 1910s to the 1940s, with roles that included Clorinda Widairs in A Lady of Quality (1913), Mrs. Sinclair in Young Sinners (1931), Grandmother Lovell in The Old Maid (1939), and Granny Tyl in The Blue Bird (1940).

Her fellow actress, Eva Moore bailed her for a surety of £100, and she was put on probation for twelve months at the Great Marlborough Street Magistrates Court.

In 1923, she left Great Britain for good, and sailed to New York City to return to Broadway and pursue a career in Hollywood.

Loftus died from a heart attack and the effects of alcoholism at the Lincoln Hotel in New York City, on 12 July 1943, aged 66.