Born in Boston, Massachusetts, to the Review Samuel Dexter, the 4th minister of Dedham, he graduated from Harvard University in 1781 and then studied law at Worcester under Levi Lincoln, Senior, the future Attorney General of the United States.
After he passed the bar in 1784, he began practicing in Lunenburg, Massachusetts. He was elected to the Massachusetts House of Representatives and served from 1788 to 1790. He was elected to the United States House of Representatives as a Federalist and served in the 3rd Congress (March 4, 1793-March 3, 1795).
He served in the United States Senate from March 4, 1799 to May 30, 1800 (the 6th Congress).
In December 1799, he delievered the Senate eulogy for George Washington. Dexter served in the Senate for less than a year, and resigned in order to accept appointment as United States Secretary of War in the administration of President John Adams.
During his time at the War Department he urged congressional action to permit appointment and compensation of field officers for general staff duty. When Secretary of the Treasury Oliver Wolcott, Junior. resigned in December 1800, Adams appointed Dexter as interim Secretary, and Dexter served from January to May, 1801.
He returned to Boston in 1805 and resumed the practice of law.
He left the Federalists and became a Democratic-Republican because he supported the War of 1812. He was an unsuccessful candidate for Governor of Massachusetts in 1814, 1815 and 1816. Dexter was an ardent supporter of the temperance movement and presided over its first formal organization in Massachusetts.
He died on May 4, 1816 shortly before his 55th birthday and is buried at Mount Auburn Cemetery in Cambridge, Massachusetts.
Samuel Dexter is the namesake of Dexter, Maine. The USRC Dexter (1830) was named in his honor.
Member Massachusetts House of Representatives from. Charlestown, 1788-1790. Member United States House of Representatives (Federalist) from Massachusetts, 3d congress, 1793-1795.
Member United States Senate from Massachusetts, December 2, 1799-June 1800.
Married Catherine Gordon, March 7, 1786, 1 son, Franklin.