He was educated at Princeton College, and came west with his family, among the first settlers in the Miami Purchase.
He was a nephew of the pioneer land speculator of southwest Ohio John Cleves Symmes. In 1794, he was appointed Hamilton County Sheriff by Territorial Governor Arthur Saint Clair. Symmes married Elizabeth Oliver on April 10, 1796 in North Bend, Ohio.
Symmes practiced law in Cincinnati, and, in June 1803, he was elected to the first Board of Directors of the first bank established in the State of Ohio, the Miami Exporting Company of Cincinnati.
In 1803 he was appointed Prosecuting Attorney for several counties. Just after statehood, Symmes was elected to represent Hamilton County in the Ohio Senate for the first through third General Assemblies, 1803-1805.
In 1805 the Ohio Legislature appointed him a judge of the Ohio Supreme Court, to fill the vacancy created when Return Jonathan Meigs, Junior. resigned
In 1808-1809, Symmes served as President of the Cincinnati Council, (equivalent to Mayor). Symmes was appointed register of the Cincinnati Land Office by President Jefferson, resigning from the court, and served for seven years.
Symmes died May 10, 1817 in Cincinnati.