Samuel Huntington was born in Coventry, Connecticut, in 1765. His father, Reverend Joseph Huntington, was a member of a prominent New England family and brother of Samuel Huntington (1731-1796), signer of the Declaration of Independence, president of the Continental Congress, and governor of Connecticut. The elder Samuel Huntington adopted the younger when he was around 7 years old, and ensured that he had a privileged upbringing. Huntington graduated from Yale in 1785 and was admitted to the Connecticut bar in 1793. He set up a practice in Connecticut and invested in land on the frontier through the Erie Company and the Connecticut Land Company.
Huntington married his cousin, Hannah Huntington, in 1791; they had six children: Francis (1793-1822), Martha D. (b. 1795), Julius C. (b.1796), Cobert (b.1797), Samuel (1799-1804), and Robert G. (1800). In 1800 he traveled to Ohio and the following year he and his family settled in the small town of Cleveland, where he owned a sizeable plot of land. They moved to a number of towns in the Western Reserve in Ohio over the next decade, and eventually founded the town of Fairport, Ohio. Huntington owned land and business interests in Ohio, including several mills in the area and over 4,000 acres along Lake Erie. Huntington also served in a number of government positions in Ohio. He was appointed lieutenant colonel of the Trumbull County militia and justice of the peace, and was elected as a delegate to the Ohio Constitutional Convention in 1802. The following year, he was elected to the state senate's first general assembly and was appointed chief justice of the state supreme court. He left his judgeship to become the third governor of Ohio, from 1808 to 1810. After his governorship, Huntington ran for United States Senate, but lost. During the War of 1812, he served as Army paymaster under William Henry Harrison. He died from an illness in 1817.