Silsbee was the eldest child of Capt. Nathaniel and Sarah (Becket) Silsbee. At the age of fourteen, to support his family upon the financial failures of his father, he went to sea and learned navigation. His able seamanship won him, at the age of nineteen, command of Elias Hasket Derby's Sloop "Sally". Silsbee continued commanding Derby vessels and had many interesting adventures and exploits with privateers, French Consuls, and such.  In 1795 he became part owner of the Schooner "Betsy" and continued to prosper and master his own vessels. In 1801 he placed his brothers, William and Zachariah, in charge of his ships. Nathaniel continued owning vessels in partnerships until the 1840s, but he actively retired from shipping when he commenced his political career.
Nathaniel married Mary Crowninshield, the daughter of one of Salem's wealthiest merchants, on December 12, 1802. Their son Nathaniel (1804-1881) was mayor of Salem from 1849-1850 and 1858-1859.
United States House of Representatives
Silsbee was elected to the United States House of Representatives (March 4, 1817 – March 3, 1821). He was chairman of the in the Twenty-first Congress. He declined to be a candidate for renomination in 1820.
United States Senate
He was elected to the United States Senate in 1826 to fill the vacancy in the term ending March 3, 1829, caused by the resignation of James Lloyd. He was re-elected in 1829 and served from May 31, 1826 to March 3, 1835. He was chairman of the U.S. Senate Committee on Commerce in the Twenty-third Congress. He was a Whig presidential elector in 1836.
Silsbee resumed mercantile pursuits in Salem, where he died; interment in The Burying Point, the second oldest cemetery in the US.
- Cooke, Harriet Ruth Waters (1889), The Driver family: a genealogical memoir of the descendants of Robert and Phebe Driver, Cambridge, MA: University Press, p. 474.
- Perkins Institute and the Massachusetts School for the Blind (1902), Seventieth Annual Report of the Trustees of the Perkins Institute and the Massachusetts School for the Blind for the year ending August 31, 1901, Boston, MA: Perkins Institute and the Massachusetts School for the Blind, p. 47.
- Curley, Jerome (February 26, 2012). "From Teen Captain to the Knights of Columbus". Salem Patch. Salem, Ma. Retrieved March 11, 2016.
- King, Caroline Howard (1937). When I lived in Salem, 1822-1866. Brattleboro, Vt.: Stephen Daye Press.
- "SILSBEE FAMILY PAPERS, 1637, 1754-1907" (PDF). Peabody Essex Museum. Retrieved March 11, 2016.
- United States Congress. "Nathaniel Silsbee (id: S000411)". Biographical Directory of the United States Congress.
|U.S. House of Representatives|
| Member of the U.S. House of Representatives
from Massachusetts's 2nd congressional district
March 4, 1817 - March 3, 1821
| U.S. senator (Class 2) from Massachusetts
May 31, 1826 - March 3, 1835
Served alongside: Elijah H. Mills, Daniel Webster
| President of the Massachusetts Senate
1823 – 1826