The department did not identify the two U.S. citizens, citing privacy concerns.
But the family of U.S.-Palestinian dual nationals Hashem Alagha, 20, and Borak Alagha, 18, say the two brothers were detained in a raid on a home west of the city of Khan Younis on Thursday morning.
Four other relatives were detained, including the brothers' Canadian father and an uncle who is mentally disabled, according to the brothers' cousin, Yasmeen Elagha, who lives near Chicago.
In a statement, a spokesperson for the State Department said it was "aware of reports of (the) detention of two U.S. citizens in Gaza and (was) seeking additional information."
The Israeli military had no immediate comment.
Israel has arrested or detained hundreds of Palestinians in Gaza since Oct. 7, when it launched its military offensive in the territory following a deadly attack in Israel by Hamas, according to the Palestinian Prisoners' Club advocacy group.
The two brothers, born in the Chicago area, have not yet been cleared to leave Gaza, Elagha said. Americans listed by the U.S. as wanting to leave Gaza at the Egyptian-controlled Rafah crossing must be approved by both Israel and Egypt.
(Reporting by Simon Lewis and Doina Chiacu; Editing by Rami Ayyub)
