Clarke was born in Harrow, England, to Joseph Thacher Clarke, an American, and his German wife, Agnes Paulina Marie Amalie Helferich. Her father was interested in music, and Clarke started on violin after sitting in on lessons that were being given to her brother, Hans Thatcher Clarke, who was 15 months her junior. She began her studies at the Royal Academy of Music in 1903, but was withdrawn by her father in 1905 after her harmony teacher Percy Hilder Miles proposed to her. He later left her his Stradivarius violin in his will. She made the first of many visits to the United States shortly after leaving the Royal Academy. She then attended the Royal College of Music from 1907 to 1910, becoming one of Sir Charles Villiers Stanford's first female composition students.