The name Nanticoke was derived from Nantego, the Indian tidewater people who moved here when their Maryland lands were spoiled for hunting by the colonial settlement in 1608.
Nanticoke was incorporated as a village in 1830; Nanticoke was chartered by the Pennsylvania Legislature as a borough on January 31, 1874.
Nanticoke experienced its greatest increase in population between 1917 and 1925 and qualified to become a Third Class City. The citizens voted in the fall of 1924 to form a city government, and elections were held the following year. The new city government consisted of a Mayor and four Councilmen who took office in January 1926, which was the official date of becoming a Third Class City.
The Concrete City, built by the Delaware, Lackawanna and Western Railroad's coal division in 1911 to house its workers, is located near the Hanover section of Nanticoke. Abandoned since 1924, it was designated an historic site in 1998, and its remains still stand as a tourist attraction. The original road that used to run to the structures has been bulldozed, though it still remains on maps. There is an alternate entrance route that does not appear on maps. It can be found at the end of Bliss & Mosier St's - Hanover section of Nanticoke
Nanticoke city officials voted unanimously to apply to the state for Act 47, or economically distressed city status, which was granted in 2006. Nanticoke faced a projected $700,000 deficit that year, with revenues flat and falling far behind expenses.