The warning came after the Israeli army said it bombed dozens of targets in Gaza from Sunday to Monday, in response to rocket fire from the strip. Palestinian medical officials said four people were wounded.
Washington regularly updates warning notices to Americans traveling to and living in countries around the world.
In the case of Gaza, the State Department warned against "all travel" to the territory and "urges those present to depart as soon as possible when border crossings are open."
It had issued a similar warning in December 2015.
Since January, 14 rockets fired from Gaza have hit Israeli territory, the military said.
The border area has remained tense since the July-August 2014 war between Israel and Gaza militants that killed more than 2,200 Palestinians and 73 people on the Israeli side.
"Gaza is under the control of Hamas, a foreign terrorist organization. The security environment within Gaza and on its borders is dangerous and volatile," the State Department said in its warning Tuesday.
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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 an AFP count shows 220 Palestinians and 34 Israelis killed since October 1, 2015 in the Palestinian territories, Jerusalem and Israel.
Most of the Palestinians killed were attackers or suspected attackers. A number were killed in clashes with the Israeli army.
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.