The two, Holli Chmela, 27, and Taylor Luck, 23, have been working for the Jordan Times and had been expected back in Amman on Saturday, the Amman-based paper's chief editor told The Associated Press.
The embassy said the two reportedly left Beirut for the northern Lebanese port of Tripoli, a predominantly Sunni Muslim city where militants and Islamic fundamentalists are known to be active. There have been sectarian fighting and bombings in recent months.
Earlier this week, the embassy issued a statement warning its citizens about potential violent actions targeting Americans in Lebanon and calling on them to be more watchful. It said the threats were particularly high in the first half of October.
Chmela and Luck arrived in Lebanon on Sept. 29 from the Jordanian capital of Amman on vacation. They told a friend on Oct. 1 that they were traveling from Beirut to Tripoli through the coastal town of Byblos that day, an embassy statement said.
They then planned to cross by land into Syria before returning to Jordan on Saturday, the embassy said.
"The families ... are asking for the public's assistance in providing information on the possible whereabouts of the two U.S. citizens," the embassy said.
Lebanese security officials told The Associated Press they are searching for Chmela and Luck and trying to ascertain whether they had left the country.
A Jordanian security official said U.S. authorities in Beirut were investigating and that Jordanian authorities are not involved.
The officials spoke on condition of anonymity because of regulations and the sensitivity of the issue.
Luck, of Oak Park, Illinois, has been a reporter at the Jordan Times for the past 18 months. He graduated last year from Beloit College in Wisconsin as an international relations major but also studied Arabic, said the school's public affairs director Ron Nief. He said the college awarded Luck a grant to return to Jordan for study.
Chmela worked as a clerk for The New York Times in Washington before leaving earlier this year to study Arabic in Jordan, according to Times' Bureau Chief Dean Baquet. In a memo to staff about the disappearance, he said she later took an internship with the Jordan Times.
She worked as an intern at the English-language daily for three months before leaving the job several weeks ago, the paper's chief editor, Samir Barhoumeh, said.
Barhoumeh said Luck, who speaks Arabic, had planned to go to visit the Syrian city of Aleppo after passing through Lebanon. He told The AP as far as he knows Luck did not enter Syria.
Luck's mother called Barhoumeh Saturday expressing concern, saying her son did not use his credit card since Oct. 1, he said.
A message left by the Associated Press at a phone listing for Luck's mother was not immediately returned Wednesday.
Chmela and Luck left their Beirut hotel Sept. 30 after a one-night stay, the hotel manager Nimr Shalala said. "They checked out, took all their belongings and didn't say anything," he told The AP.
The U.S. Embassy said it was coordinating efforts with the State Department in Washington and embassies in Amman and Damascus.