Pomerene studied law at Princeton University and the University of Cincinnati. In 1886 he began in Canton ( Ohio) to work as a lawyer. After having worked in a variety of cities, counties and state agencies as a lawyer and prosecutor, he was elected in 1910 to the Lieutenant Governor of Ohio. A post he retained until 1911, but only because he was elected to the U.S. Senate. In 1916 he won the election for a second term, but then lost in the election for a third term. In the Senate he was chairman of the Committee on Civil Service and Retrenchment, of the Committee on Privileges and Elections and the Committee on Corporations Organized in the District of Columbia.
In 1924 he was designated by President Calvin Coolidge as a special prosecutor to investigate the " Teapot Dome " facts. The case went to the Secretary of the Interior Albert B. Case, had forgiven the oil drilling rights in Wyoming unlawfully.
1928 Pomerene failed in the nomination as the Democratic candidate for the election of the U.S. president.