A handsome and sophisticated young man, Wilfred Lucas headed to New York City to work in the theater, making his Broadway acting debut in 1904 at the Savoy Theater in the production of The Superstition of Sue. Following his 1906 role in the highly successful play, The Chorus Lady, Lucas was recruited to the fledgling Biograph Studios by the still struggling D. W. Griffith. At the time, the film business was still looked down upon by many members of the theatrical community who refused to "lower" themselves and work in film or to help an industry that was seen as a competitive threat. In her 1925 book titled When the Movies Were Young, Griffith's wife, actress Linda Arvidson, told the story of the early days at Biograph Studios. In it, she referred to Wilfred Lucas as the "first real grand actor, democratic enough to work in Biograph movies."

In 1908, Wilfred Lucas made his motion picture debut in Griffith's production, The Greaser's Gauntlet. He appeared in more than fifty of these short films (usually 17 minutes) over the next two years and in 1910, while still acting, he wrote the script for Griffith's film Sunshine Sue which was followed by many more scripts between then and 1924. Lucas also began directing in 1912, first with Griffith on An Outcast Among Outcasts, and during the ensuing twenty years directed another 44 films. In 1916, Lucas appeared in Griffith’s film, Intolerance, a monumental project regarded by many as the most spectacular film of all time.

Part of the group of Canadian pioneers in early Hollywood, Lucas became friends and sometimes starred with Mary Pickford, Sam De Grasse, and Marie Dressler. Canadian born director Mack Sennett hired him to both direct and act in a large number of films at his Keystone Studios.

While working at Biograph Studios, Wilfred Lucas met and ultimately married actress/screenwriter Bess Meredyth (1890-1969) with whom he had a son. John Meredyth Lucas (1919-2002) became a successful writer and director including a number of episodes of the famous Mannix and Star Trek television shows. The divorce was a bitter one and through what is now known as Parental Alienation Syndrome (PAS), Wilfred Lucas became estranged from his son.

Wilfred Lucas was one of the fortunate ones whose skills and voice allowed him to make the successful transition from silent film to sound. While working in Hollywood, in 1926 he returned to the stage, performing in several Broadway plays.He later appeared as a foil for Laurel and Hardy,in their feature films Pardon Us and A Chump at Oxford.

During his long career, Wilfred Lucas appeared in more than 375 films. Although for a time he was cast in leading roles, he became very successful as secondary and minor characters, making a good living in the film industry for more than three decades.