Mr Obama becomes the first serving US president to visit since Lyndon Johnson in 1966 as he tours Asia to fortify alliances amid concern over China's rise and push his troubled plans for a Pacific-wide trade pact.
He left Soeul on Saturday for Malaysia on the third leg of his tour of Asia.
Washington is keen to emphasise its relations with economically successful, moderate-Muslim Malaysia as the United States battles image problems in the Islamic world.
But Malaysia is a close trading partner of China and has resisted key aspects of Mr Obama's Trans-Pacific Partnership agreement on trade.
Mr Obama also will have to tread a fine line between courting Prime Minister Najib Razak while acknowledging huge segments of society in multi-cultural Malaysia that are fed up with his corruption-plagued coalition which has been in power for 57 years.
Mr Najib craves acceptance abroad, where he portrays himself as a reformer and religious moderate.
But the reality is one of a "corrupt and authoritarian regime," opposition leader Anwar Ibrahim said in a statement Saturday that urged Mr Obama to voice support for "freedom and democracy" in Malaysia.
"It would be an opportune moment to live up to the ideals Obama espoused in his campaign and the early days of his administration," Mr Anwar said.
Mr Najib's government has come under growing criticism for harassing opponents and stifling free expression, particularly after elections last year in which it lost the popular vote to Mr Anwar's opposition.
Mr Najib clung to power via what critics say is a skewed electoral system favouring his coalition.
Mr Anwar was convicted March 7 and sentenced to five years in jail on controversial sodomy charges that he says are politically motivated and which the US State Department has questioned.
A number of other activists, opposition politicians and rights groups face a range of charges including sedition, while Christians complain of official intimidation.
In an interview with government-controlled The Star newspaper published Saturday, Mr Obama said mildly that the most successful countries are those that "uphold the human rights of all their citizens, regardless of political affiliation, ethnicity, race or religion".
Mr Obama will not see Mr Anwar -- National Security Advisor Susan Rice will -- but he will meet late Sunday with representatives of several groups critical of the government.
During the visit, Mr Obama is expected to stress growing security ties with Malaysia, which is among several nations with competing territorial claims in the South China Sea, where Beijing's assertiveness has sparked alarm.
Mr Najib is believed to be keen for a dose of Mr Obama's star power in the face of domestic criticism and the loss of MH370 which disappeared en route from Kuala Lumpur to Beijing.
His government has come under international criticism over the missing plane and a response that has been seen as secretive and incompetent.
Mr Obama will meet Malaysia's king on Saturday and attend a state dinner.
On Sunday, he visits the National Mosque in Kuala Lumpur and holds a bilateral meeting with Mr Najib, before a "town hall" meeting with youth leaders from around Southeast Asia.
He leaves Monday morning for a visit to the Philippines.