Ross was born in Ashland, Ohio. He worked in the newspaper business, first in Ohio, then in Milwaukee, Wisconsin and Topeka, Kansas.

After the death of James H. Lane in 1866, Ross was appointed to the United States Senate. Ross is known for casting the decisive vote which acquitted Andrew Johnson during his 1868 Presidential Impeachment trial. Some people have claimed that Ross voted against the conviction due to concerns about his colleague Samuel C. Pomeroy receiving patronage from Benjamin Wade. They also claim that Ross used his vote as a means to receive favors from Johnson. Others claim Ross cast his vote because the man whom President Johnson fired, Edwin M. Stanton, was hired during Lincoln's Presidency, which clears Johnson of any crime (this would the most reasonable reason for the vote, considering that is what the trial was about). Ross lost his bid for re-election in 1870. From 1885 to 1889, he served as governor of New Mexico Territory.

Edmund G. Ross is one of eight U.S. Senators featured in Profiles in Courage, the 1956 Pulitzer Prize-winning history written by then-Senator John F. Kennedy in commemoration of past acts of political courage in Congress.