Charles Denison was born on January 23, 1838 in Kingston, Pennsylvania to a prominent Luzerne County family.  His grandfather was second in command of American forces in the battle of Wyoming Valley, and his uncle, George Denison, served in Congress.  Charles Denison was educated locally and then entered Dickinson College with the class of 1838 when it reopened in 1834 under Methodist auspices.  He was elected as a member of the Union Philosophical Society and studied law after he graduated.

Denison was admitted to the Pennsylvania bar in 1840 and opened a practice in Wilkes-Barre.  He was elected as a Democrat to Congress three times from the 12th District of Pennsylvania, serving from 1863 to 1867 in the 38th, 39th, and 40th Congresses. Denison was also a Pennsylvania delegate to the 1864 Democratic National Convention in Chicago that nominated George McClellan for president and endorsed a negotiated peace with the Confederate States.

Charles Denison died in office at home in Wilkes-Barre on June 27, 1867 and was buried in the Forty Fort Cemetery in Kingston.  He was forty-nine years old.