In 1812, Barstow moved to Tioga County, and there worked at his father's farm and taught school. Within a year he had become good friends with Judge Coryell (a powerful and influential figure in local politics) and by 1813 had married the Judges' daughter Nancy. He then built the first frame house in the town of Nichols, and opened a store at this location.
Barstow was a member of the New York State Assembly (Tioga Co.) in 1816, 1816-17 and 1818. He was First Judge of the Tioga County Court from 1818 to 1823, and at the same time a member of the New York State Senate (Western D.) from 1819 to 1822, sitting in the 42nd, 43rd, 44th and 45th New York State Legislatures. By 1823, he was ready for a bigger house so he bought a parcel of land and built a magnificent two-story brick New England style home which now, 175 years later, houses the current establishment, The Barstow House Restaurant.[1] He was again a member of the State Assembly in 1824 and 1827. He was New York State Treasurer from 1825 to 1826. In 1830, he was Town Supervisor of the Town of Nichols.
Elected as an Anti-Mason to the 22nd United States Congress, Barstow was U.S. Representative for the twenty-fifth district of New York from March 4, 1831, to March 3, 1833.
In 1836, he was the Whig candidate for Lieutenant Governor of New York on the ticket with Jesse Buel, but they were defeated by the incumbent Governor Marcy and Lt. Gov. John Tracy. Barstow was again State Treasurer from 1838 to 1839. Afterward, he continued the practice of medicine and engaged in agricultural pursuits in Nichols, New York, where he died on March 30, 1865, aged 80. He was buried at the Ashbury Cemetery there.