She made her film debut in 1908 with a short film called the "Fatal Hour" directed by D. W. Griffith. For the next year she acted in many controversial roles in which she had to portray ethnicities other than her own. MacPherson had dark hair, so she was often cast in gypsy or Spanish roles. From 1908 to 1917, she racked up 146 acting credits. She was quoted as looking back on her time with Griffith as her "first glimmer of the possibilities in the new industry from those days on [she had seen a variety of attitudes toward the script writers."