Samuel Dexter was born in Boston, Massachusetts, on May 14, 1761, and graduated from Harvard University. Dexter, a lawyer by profession, began his career in public service as a member of the Massachusetts House of Representatives (1788-1790). Three years later, he gained a seat in the U.S. House of Representatives (1793 -1795) as a member of the Massachusetts delegation; he would later hold a seat for two years in the U.S. Senate (1799-1800).In 1800, Dexter accepted an offer from President John Adams to join his cabinet as secretary of war. By the end of the year, Dexter found himself fulfilling the duties of treasury secretary and secretary of state as well, a convenient solution for the final months of the Adams presidency.

With the arrival of the Jefferson administration in 1801, Dexter retired from politics and resumed the career in law he had first practiced as a young man from 1784 to 1788. After turning down numerous offers to serve the United States as a foreign minister during the presidency of James Madison, Samuel Dexter died in Athens, New York, on May 3, 1816.