The shooting occurred at about 9pm on Wednesday (01:00 GMT, Thursday) near the Capital Jewish Museum in Washington, DC, according to authorities.
The Israeli Foreign Ministry named the two victims as Yaron Lischinsky and Sarah Lynn Milgrim.
Pamela A Smith, the chief of the Metropolitan Police Department, stated authorities had detained a single suspect over the shooting, identified as 30-year-old Elias Rodriguez of Chicago, Illinois.
“Prior to the shooting, the suspect was observed pacing back and forth outside of the museum. He approached a group of four people, produced a handgun and opened fire, striking both of our decedents,” Smith said at a news conference.
Smith added Rodriguez chanted, “Free, free, Palestine”, while in custody.
Smith did not elaborate on a suspected motive for the attack.
Washington, DC Mayor Muriel Bowser told reporters her administration would not tolerate “violence or hate in our city”.
“We will not tolerate any acts of terrorism, and we’re going to stand together as a community in the coming days and weeks to send a clear message that we will not tolerate anti-Semitism,” Bowser added.
The American Jewish Committee, which had hosted an event at the museum, announced it was “devastated that an unspeakable act of violence took place outside the venue”.
US President Donald Trump has also expressed condolences to the families of the victims, and stressed the killings were “based obviously on antisemitism”.
“Hatred and Radicalism have no place in the USA,” Trump said on Truth Social, adding, “Condolences to the families of the victims. So sad that such things as this can happen! God Bless You ALL!”
US Secretary of Homeland Security Kristi Noem said federal authorities were investigating the attack and would bring its “depraved perpetrator” to justice.
Israel’s Ambassador to the United Nations Danny Danon called the shooting a “depraved act of anti-Semitic terrorism”.
“Harming the Jewish community is crossing a red line,” Danon said.
Israeli Prime Minister Benjamin Netanyahu said he has instructed Israeli missions around the world to beef up security after the attack.
Israel’s Foreign Minister Gideon Sa’ar has also stated he is “very worried” about more attacks on diplomatic missions around the world following the incident.
“I have been worried for the past few months that something like this would happen and it did, and the list of fallen foreign service members has grown today,” Sa’ar said, speaking at a news conference in Jerusalem on Thursday.
He also added there have been a number of attacks and attempted attacks on Israeli missions around the world, many of which he says have not been reported.