Born on a farm near Harrod, Ohio, to Henry and Barbara (Herring) Fess, he was educated in country schools and graduated at Ohio Northern University (ONU) of Ada in 1889 and married Eva C. Thomas the following year.

He served as chairman of the Committee on the Library during Sixty-ninth through Seventy-second Congresses, and as Republican Whip from 1929 to 1933.

After his appointment, the Cincinnati Enquirer referred to Fess as a "party wheelhouse and stand patter of the most approved type," and added "It was Senator Fess's proven ability not only to defend, but to eulogize, the acts of Republican administrations, no matter how unpopular they may be, that led to his selection as national chairman.

That speech, a month before the presidential election, was delivered to just 150 listeners,[2] a sign of the Republican Party's problems in mid-Depression.

He died in Washington, D.C. at the age of 75 and was interred at Glen Forest Cemetery in Yellow Springs, Ohio.