During a press availability before a meeting with Jordan's King Abdullah at the White House, Obama said he has yet to see "confirmation and strong evidence" chemical weapons have been used.
"What we have right now is an intelligence assessment," Obama said, adding the United States is working with allies "to obtain more direct evidence."
"In the meantime, I've been very clear publicly, but also privately, that for the Syrian government to utilize chemical weapons on its people crosses a line that will change my calculus of how the United States approaches these issues," Obama said.
The White House said in a letter to congressional leaders this week the nation's intelligence agencies assessed "with varying degrees of confidence" the Assad regime used the chemical agent sarin on a small scale.
McCain said Washington should set up a Syria no-fly zone as a result of the assessment.
"The president of the United States said that if [Syrian President Bashar Assad] used chemical weapons, it would be a game changer -- that it would cross a 'red line' -- and it's pretty obvious that red line has been crossed," McCain was quoted by The Wall Street Journal as saying.
"Now I hope the administration will consider what we have been recommending now for over two years of this bloodletting and massacre, and that is to provide a safe area for opposition to operate, to establish a no-fly zone and provide weapons to the people in the resistance who we trust," McCain said.
The senators had asked the White House whether Assad or his supporters had used chemical weapons during the 2-year-old war, as Israel claims.
The White House said it had strong indications chemical weapons were used.
U.S. Secretary of State John Kerry told senators there may have been two instances of chemical weapons use by the regime.
"Given the stakes involved, and what we have learned from our own recent experience, intelligence assessments alone are not sufficient," said the White House letter, signed by Legislative Director Miguel Rodriguez.
The "recent experience" was an allusion to faulty intelligence in Iraq that led to the 2003 U.S. invasion of Iraq.
The Syrian Network for Human Rights said it documented 199 deaths due to violence in Syria Friday, including 13 children, 15 women, seven victims tortured to death and 34 armed rebels killed.
The organization said 18 people were killed in and around Damascus, 18 in Hasaka, 18 in Homs, 17 in Idlib, 13 in Aleppo, 12 in Daraa and 10 each in Hama and Dier Alzoor.