McCain said he was "sure and confident" that al-Assad had used chemical weaponry before, and that Barack Obama's failure to act on what the U.S. president had said would be a "red line" had given the Syrian leader a green light to use these weapons again.
McCain called for the United States to take military action from outside Syria's borders to prevent that happening, saying it could "very easily" do what's needed to take out Syrian runways and aircraft and establish a no-fly zone.
Witness: Convulsions, trouble breathing
The Syrian civil war has killed more than 100,000 people and displaced millions, according to the United Nations.
There have been repeated allegations that chemical weapons were being used during the course of the conflict.
The latest alleged attack took place in eastern and western Ghouta, rebel strongholds that the regime has been fighting to take back for more than a year.
Initially, Syrian opposition groups claimed that hundreds were killed Wednesday, but as the day wore on, the number went up -- more than 1,300 people, according to the opposition Local Coordination Committees and the Syrian National Council. The council is an umbrella group of anti-regime activists.
Video posted Wednesday shows people carrying limp bodies, some haphazardly covered in sheets, others splayed, nearly nude, on the floor. A man is on his back, staring blankly upward, his chest convulsing violently. Others hold tissues to their mouth, appearing to gag.
Dr. Abu Said at a field hospital in Sakba, east of Damascus, told CNN how the injured started streaming in shortly after predawn prayers Wednesday. Forty of the 200 people brought to the field hospital died, Said said.
A man who referred to himself as a volunteer first responder, Abu Gazi, said he was with a doctor at a field hospital in Arbeen who reported 300 people dead and 500 wounded.
The symptoms, he said, included unconsciousness, foaming from the nose and mouth, constricted pupils, fast heartbeat and difficulty breathing. People died of asphyxiation, he said.
"The inspectors will not come," said a resident who didn't want his name used. "If they wanted to come, they would have come a long time ago.
"The Assad regime determines where the inspectors go, and they will not let them go there. There is already a siege around eastern Ghouta from the Assad regime."
'Held to account'
Rights group Human Rights Watch also called Wednesday for the U.N. inspection team to be given immediate access to the area.
"Whether or not chemical weapons were used, the attack left a large number of civilians dead, and those responsible for unlawful killings should be held to account," it said.
U.N. children's agency UNICEF said the reports of Wednesday's attack on civilians were deeply disturbing and that those who failed to protect children must be held accountable.
Syria's official news agency, SANA, quoted Iranian Foreign Minister Mohammad Javad Zarif on Thursday as saying the rebels must be behind any chemical weapons attack, if confirmed, as "they do not hesitate to commit any crime."
Russian officials, meanwhile, dismissed the claims of chemical weapons as a "provocation planned in advance," Russian Foreign Ministry spokesman Alexander Lukashevich told Interfax news agency. He suggested it was timed to coincide with the visit by the U.N. team.