"Clinton will travel to France, Japan, Mongolia, Vietnam, Laos, Cambodia, Egypt and Israel departing Washington, DC on July 5," said a statement from State Department spokeswoman Victoria Nuland released upon their departure.
Clinton was officially invited to Laos by counterpart Foreign Minister Thongloun Sisoulith in 2010 when he made the first visit by a top Laotian official to Washington since Soviet-backed communist rebels swept to power and replaced the monarchy there in 1975.
US relations with Laos, while never severed, were long tense, in part over its campaign against the Hmong hill people who assisted US forces during the Vietnam War, along with uncertainties over American troops missing in action.
But the United States established normal trade ties with Laos in 2004 and has recently looked at ways to help clean up abandoned ordnance that continues to take a heavy civilian toll.
US forces dropped millions of bombs on the country to cut off North Vietnam supply lines, which according to a 2010 survey have killed or injured some 50,000 people in Laos.
The Laos stop forms part of an Asian swing that will also take in Japan, Mongolia and Vietnam ahead of talks in Cambodia with the Association of Southeast Asian Nations (ASEAN) and regional powers including China.
On her way back from Asia, Clinton will make a two-day stop in America's key Middle Eastern ally Egypt, her first since President Mohamed Morsi of the Muslim Brotherhood became the country's first Islamist leader.
Her last visit to Egypt came in March 2011, when she toured Cairo's Tahrir Square in the wake of the protests that ousted Hosni Mubarak.
Clinton wraps up her tour with a final two-day stop on July 16-17 in Israel, "where she will be meeting with the Israeli leadership to discuss peace efforts and a range of regional and bilateral issues of mutual concern," according to Nuland's statement.
It will be Clinton's first visit to Israel in almost two years, since September 2010.
"We can presume she will be visiting multiple sites in Israel," Patrick Ventrell, a State Department spokesman, told journalists in Washington.
Her opening stop though was France on Thursday for talks boycotted by both China and Russia on how to end the 16-month conflict in Syria.
Friday's "Friends of Syria" meeting is aimed at coordinating efforts to stop the violence in the country that the London-based Syrian Observatory for Human Rights says has claimed the lives of 16,500 people.
While in Paris, Clinton will also meet Palestinian leader Mahmud Abbas to discuss efforts to build trust with the Israelis following an exchange of letters between Abbas and Israeli Prime Minister Benjamin Netanyahu, the State Department said.
Observers say Clinton's brief talks in Laos are likely to focus on the US administration's Lower Mekong Initiative as well as efforts to fight drug trafficking. She may also seek to give fresh impetus to American hopes to recover the remains of US troops killed there during the Vietnam War.
The talks could also focus on Laos's imminent entry to the World Trade Organization.
In May, Laos said it had postponed construction of a controversial dam on the Mekong, dismissing fears the work was going ahead despite growing regional and international opposition.
The $3.8 billion Xayaburi dam is slated to be the first of 11 big dams along the main stem of the 4,600 kilometer (2,850 mile) Mekong River, which passes through China, Myanmar, Laos, Thailand, Cambodia and Vietnam.
Laos is one of the poorest nations in the world, with just 6.5 million people, and sees hydropower as vital to its potential future as the "battery of Southeast Asia," selling electricity to its more industrialized neighbors.
But activists say the dam projects could spell disaster for the roughly 60 million people who depend on the Mekong waterway -- the world's largest inland fishery.
President Barack Obama's administration launched the Lower Mekong Initiative in hopes of supporting the environment, health and education in the populous region as part of a renewed effort to build relations with Southeast Asia.
It was unclear if Clinton would also raise the issue of the Hmong minority during her trip.
Some 250,000 Hmong have resettled in the United States and often speak of persecution in Laos, enlisting support of US lawmakers to pressure the Vientiane government.