Americans urged to leave Gaza while 'borders are open'
The warning signals an escalation in Israeli violence, after occupying forces carried out a continuous bombing campaign on Gaza from Sunday to Monday, in response to alleged rocket fire from the strip.
Palestinian medical officials said at least four people were wounded.
While Washington regularly issues warning notices to Americans traveling to and living Gaza, it urged its nationals to "depart as soon as possible when border crossings are open," signalling towards the potential closure of Gaza borders amid an escalation of violence.
Since January, 14 rockets fired from Gaza have hit Israeli-held territory, the military said.
In July, Israeli air raids hit four sites in Gaza after a rocket struck a building in Sderot.
Palestinian militants in Gaza and Israel have fought three wars since 2008, including the most recent conflict in the summer of 2014 that killed 2,251 Palestinians and 73 Israelis.
The border area has since remained tense.
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"Gaza is under the control of Hamas, a foreign terrorist organisation. The security environment within Gaza and on its borders is dangerous and volatile," the State Department said in its warning Tuesday.
As for Israel and the West Bank, a wave of violence there since October 2015 has left Americans dead and wounded, the department said.
However, "there is no indication that US citizens were specifically targeted based on nationality."
The violence has eased in recent weeks, but more than 220 Palestinians and 34 Israelis were killed since October in the Palestinian territories, Jerusalem and Israel.
The State Department on Tuesday also condemned plans, reported by Israeli media, to expand a Jewish military compound in the West Bank city of Hebron by building homes for settlers.
"If these reports are true... that would represent a deeply concerning step of settlement expansion on land that is at least partially owned by Palestinians," department spokesman Mark Toner said at a press briefing.
"We strongly oppose all settlement activity, which is corrosive to the cause of peace. And we've said repeatedly such moves are not consistent with Israel's stated desire to achieve a two-state solution," Toner added.
Washington regularly condemns its ally Israel for illegitimate settlements in the Palestinian territories.
Agencies contributed to this report.