His plane landed in the former capital Yangon, where he will meet President Thein Sein, a former junta member who has spearheaded reforms since taking office in March 2011, and opposition leader Aung San Suu Kyi, who led the struggle against military rule and, like Obama, is a Nobel Peace Prize laureate. She is now a lawmaker.
Obama's trek to Myanmar is meant to highlight what the White House has touted as a major foreign policy achievement -- its success in pushing the country's generals to enact changes that have unfolded with surprising speed over the past year.
But some international human rights group object to the Myanmar visit, saying Obama is rewarding the country's government for a job they regard as incomplete.
Speaking in Thailand on the eve of his landmark visit to the former pariah state, Obama denied he was going there to offer his "endorsement" or that his trip was premature.
Instead, he insisted his intention was to acknowledge that Myanmar, also known as Burma, had opened the door to democratic change but there was still much more to do.
"I don't think anybody is under the illusion that Burma's arrived, that they're where they need to be," Obama told a news conference as he began a three-country Asian tour, his first trip abroad since winning a second term.
"On the other hand, if we waited to engage until they had achieved a perfect democracy, my suspicion is we'd be waiting an awful long time," he said.
The Myanmar visit, less than two weeks after his re-election, is the centrepiece of a trip aimed at showing Obama is serious about shifting the U.S. strategic focus eastwards as America winds down wars in Iraq and Afghanistan. The so-called "Asia pivot" is also meant to counter China's rising influence.
But Obama arrives with his attention divided as he faces a mounting conflict in the Gaza Strip and grapples with a looming fiscal crisis at home.
"Obama's trip to Burma risks providing an undeserved seal of approval to the military-dominated government that is still violating human rights," Brad Adams, Asia director at Human Rights Watch, said before the president arrived in the region.
Obama's aides said he was determined to "lock in" democratic changes already under way but will also press for further action, including freeing remaining political prisoners and stronger efforts to curb ethnic and sectarian violence.
A senior U.S. official said Obama would announce the resumption of U.S. aid programmes in Myanmar during his visit, anticipating assistance of $170 million in fiscal 2012 and 2013, but this, too, would be dependent on further reforms.
"The president will be announcing that the United States is re-establishing a USAID mission in Burma, which has been suspended for many years," the official told reporters in Bangkok, declining to be named.
"Our continued ramping-up of our efforts within Burma is contingent upon the government continuing to address the issues at hand on political reform, on national reconciliation and on a development that reaches their people," the official added.
The United States has softened sanctions and removed a ban on most imports from Myanmar in response to reforms already undertaken, but it has set conditions for the full normalisation of relations, such as the release of all political detainees.
Late on Sunday, state television in Myanmar said 66 more prisoners would be released on Monday, bringing to 518 the number released over the past week.
The previous batch did not appear to include any political prisoners, but a senior prison department official, who declined to be identified, told Reuters that Myint Aye, a prominent human rights activist, would be among those freed on Monday.
In a speech to be given at Yangon University to an audience that will include several high-profile former prisoners, Obama will stress the rule of law and allude to the need to amend a constitution that still gives a great role in politics to the military, including a quarter of the seats in parliament.
"America may have the strongest military in the world, but it must submit to civilian control. As president and commander-in-chief, I cannot just impose my will on our congress, even though sometimes I wish I could," he will say.
"I appoint some of our judges, but I cannot tell them how to rule, because every person in America, from a child living in poverty to the president, is equal under the law."
He looks forward to a future "where national security is strengthened by a military that serves under civilians, and a Constitution guarantees that only those who are elected by the people may govern".
Violence between majority Buddhists and the Rohingya Muslim minority in western Myanmar is a top concern, and Obama's aides said he would address the issue directly with Myanmar's leaders.
Myanmar considers the Rohingya Muslims to be illegal immigrants from neighbouring Bangladesh and does not recognise them as citizens. A Reuters investigation into the wave of sectarian assaults painted a picture of organised attacks against the Muslim community.
At least 167 people were killed in two periods of violence in Rakhine state in June and October this year.
Obama did not refer to this in the copy of his speech released to media ahead of delivery, but he will recall the sometimes violent history of the United States, its civil war and segregation, and say hatred could recede with time.
"I stand before you today as president of the most powerful nation on Earth, with a heritage that would have once denied me the right to vote. So I believe deeply that this country can transcend its differences, and that every human being within these borders is a part of your nation's story," he will say.
Thein Sein, in a letter to U.N. Secretary-General Ban Ki-moon last week, promised to tackle the root causes of the problem, the United Nations said.
Despite human rights concerns, the White House sees Myanmar as a legacy-building success story of Obama's policy of seeking engagement with U.S. enemies, a strategy that has made little progress with countries such as Iran and North Korea.
Obama's visit to Myanmar, sandwiched between stops in Thailand and Cambodia, also fits the administration's strategy of trying to lure China's neighbours out of Beijing's orbit.
For Obama, the visit carries added significance. He received his Nobel Peace Prize less than a year after taking office in 2009. The award was widely seen as recognising him more for lofty speech-making than for any major accomplishment on the world stage. This is a chance to tout a foreign policy success.
(Reporting By Matt Spetalnick; Editing by Alan Raybould and Alex Richardson)