The White House has repeatedly insisted that Syria only agreed to forfeit its chemical weapons after the credible threat of a military strike from the United States, and said that the administration could still launch an attack if Syria renegs on the agreement.
But the president had struggled to convince lawmakers and voters to back a military strike, casting the credibility of that warning into doubt.
On Tuesday, Obama said the "international dynamic" had changed.
"There were a number of allies in European countries who said, 'We want to respect the U.N. process,'" Obama said. "Well, the U.N. process has now played itself out, the investigators have unequivocally said that chemical weapons were used, and when you look at the details of the evidence they present, it is inconceivable that anybody other than the regime used it.”
The president also said the findings of the U.N. report "changes international opinion on this issue."
But while Obama pledged he was dedicated to finding a diplomatic solution, he said the agreement did not mean that the White House preferred that Assad stay in power.
"I don't think that anybody in the world community should accept the notion that somebody who kills tens of thousands of his own people, including children, women, defenseless civilians is the preferable ruler of any country," Obama said. "And I do continue to believe that it is in the interest, most importantly of the Syrian people, but also the region, if you have somebody other than Assad in that country."
Obama said he also hoped to convince Iran to abandon its nuclear weapons program through diplomacy, acknowledging that there had been "some exchanges" with Tehran.
On Tuesday, Iranian leader Ayatollah Ali Khamenei signaled that the country's newly elected, moderate president Hassan Rouhani could offer concessions in negotiations over Iran's nuclear program. The country has been hard-hit by western sanctions designed to discourage the pursuit of nuclear weapons.
Obama said there were indications Rouhani "is someone who is looking to pen dialogue with the West and with the United States in a way that we haven't seen in the past."
"And so we should test it," Obama said.