One of six siblings born to actors Greenberry Carr "Greene" Germon and Jane (née Anderson) Germon, her father was the first to perform the role of Uncle Tom at the Troy Museum in the George Aiken adaptation of Uncle Tom's Cabin produced by George C. Howard.

[1] Her mother, Jane, a cousin of actor Joe Jefferson, began her career at age 8 and continued for 50 years.

[2] Effie Germon's theatrical debut was made at the Holliday Street Theatre in Baltimore, Maryland, during the 1857–58 season.

A week earlier, Germon was present when John Wilkes Booth came into the office of Hess and inquired as to when Lincoln would attend a performance of Aladdin.

[citation needed] A photo of Germon was found on Booth when he was shot dead at Richard H. Garrett's farm in 1865.