Kerry met with Cambodian Prime Minister Hun Sen, now Asia's longest serving ruler, where he tried to balance growing economic ties between the United States and Cambodia with concerns about human rights and treatment of government critics.
He also met with Foreign Affairs Minister Hor Namhong and opposition and civil society leaders.
Kerry praised Cambodia's "remarkable" growth and modernization and the trade relationship between the two countries.
"I think its quite remarkable that the United States is, in fact, Cambodia's largest export market even though we have half the world between our countries," Kerry said. "And we will continue to explore ways to deepen our trade and investment relationship, including by helping to tackle corruption and exploring ways to strengthen Cambodia's legal institutions."
Kerry's forward-looking comments come as the Obama administration is seeking to strengthen its partnership with the 10-member Association of Southeast Asian Nations, known as ASEAN.
Cambodia, close Chinese ally
Next month Obama will host the 10 leaders of ASEAN in California. In addition to strengthening political and economic ties, the United States wants ASEAN to show more unity in response to China's growing assertiveness in the South China Sea, as Beijing steps up its building of islands and airstrips in disputed maritime areas.
Cambodia is viewed as one of China's closest allies in southeast Asia and Washington has been frustrated by it's reluctance to press China over its actions in the South China Sea. Washington saw Cambodia's chairmanship of the ASEAN block as divisive and harmful to U.S. efforts to balance Chinese influence in the region.
"The United States take pride in its history as an Asia-Pacific nation," Kerry said. "We are deeply committed to our partnership with Cambodia and with all the members of ASEAN on a regional and global basis."
Kerry came to Cambodia from Laos, which holds this year's chair of the ASEAN block, and where President Obama will make a landmark visit for the leaders summit this fall.
As part of its deepening involvement in the region, the United States has initiated a series of programs for Southeast Asia's poorest countries along the Mekong River, including Cambodia, to improve their infrastructure, health and education systems.
Kerry, a Vietnam vet, said the United States was also trying to help Cambodia clear unexploded ordnance left behind from the Vietnam War.
"We want to work with Cambodia, not just to eliminate the painful reminders of the long war, but to define a future which is very, very different and distant from that war," he said.
Kerry also met with opposition and civil society leaders as a show of continued concern about the government's treatment of its political opposition as Cambodia looks toward elections next year.
Before his visit local and international NGO groups urged the United States not to sign any new bilateral agreements until Cambodia makes efforts to improve its record on democracy and human rights.
"Friends need to talk to friends," he said. "In my discussions today, I emphasized the essential role that a vibrant, democratic system plays in the development of a country and the legitimacy of its political system. Democratic governments have a responsibility to ensure that all elected representatives are free to perform their responsibilities without fear of attack or arrest."
Shadows of the Khmer Rouge
As a senator Kerry was heavily brokering talks on creating the tribunal, known as the ECC, to bring Khmer Rouge leaders to justice for their reign of terror that killed 1.7 million Cambodians between 1975 to 1979.
"Cambodia's journey has long been personal for me," Kerry said during remarks in the garden of the renown Raffles hotel, featured in the movie "The Killing Fields" as the last refuge for foreign journalists before the Khmer Rouge forced all foreign nationals into the French embassy.
Kerry also visited the National Museum of Cambodia, which houses several Khmer artifacts returned to the country from the United States, where it was smuggled illegally after the war.
From Cambodia, Kerry travels to Beijing, where he will press Chinese leaders to step up pressure on North Korea in response to its nuclear test earlier this month and discuss concerns about China's actions in the South China Sea.