He was born in Little Britain, Orange County, New York, but moved to Newburgh, New York, at an early age and attended the Newburgh Academy. Then he studied law. He entered the United States Army at the beginning of the War of 1812 as First Sergeant of Newburgh Company Number Five. He was commissioned a captain in the Forty-first Regiment, United States Infantry, on August 15, 1813. After the war he resumed the study of law, and was admitted to the bar in Newburgh, New York on January 11, 1816. He moved to Ithaca, New York in 1818, and engaged in the practice of law.
Humphrey was elected as an Adams candidate to the Nineteenth Congress, and served from March 4, 1825 to March 3, 1827.
He was a member from Tompkins County of the New York State Assembly from 1834 to 1836, when he was active in studying prison reform as well as education, and in 1842, and was Speaker in 1835 and 1836.
He was appointed clerk of the New York Supreme Court in 1843 and held that position until 1847.
Humphrey married Ann Eliza Belknap (1797–1861) in Newburgh, New York in 1916. The couple had seven children, three of whom survived to adulthood: William Ross Humphrey (1820–1901), Charles D. Humphrey (1832–1870), and Sarah B. Humphrey Judd (1835–1904). 
- "Finding Aid to the Charles Humphrey Papers, 1810–1849". New York State Library. New York State Library. Retrieved 24 September 2014.
- Gannett, Henry (1905). The Origin of Certain Place Names in the United States. Govt. Print. Off. p. 163.
- Charles Humphrey at the Biographical Directory of the United States Congress Retrieved on 2009-5-16
-  Political Graveyard
-  Google Books = John Stilwell Jenkins: History of Political Parties in the State of New-York (Alden & Markham, Auburn NY, 1846)
Selkreg, John H, Landmarks of Tompkins County, New York. Syracuse: D. Mason & Company, 1894.
|United States House of Representatives|
|Member of the U.S. House of Representatives
from New York's 25th congressional district
William Baker, Jr.
|Speaker of the New York State Assembly