"This is not the time for armchair isolationism. This is not the time to be spectators to a slaughter. Neither our country nor our conscience can afford the cost of silence," Kerry insisted before the Senate Foreign Relations committee.
He warned that other countries such as Iran and North Korea, under fire for its suspect nuclear programs, were closely watching.
"They are listening for our silence," Kerry intoned, during a sometimes heated debate with his former Senate colleagues.
His words were echoed by US Defense Secretary Chuck Hagel, who said a US refusal to act after Obama had clearly set chemical weapons use as a "red line" would undermine America's credibility abroad.
"The word of the United States must mean something. It is vital currency in foreign relations and international and allied commitments," Hagel stressed.
At earlier White House talks with congressional leaders, Obama said he hoped for "prompt" Congressional votes next week on authorizing "proportional" and "limited strikes" against Syria.
House Speaker John Boehner and House Majority Leader Eric Cantor -- key Republicans who have had frosty relations with Obama on domestic policy -- both said they would support his plan.
"This is something that the United States as a country needs to do," Boehner said, calling on Republican colleagues to follow his example.
But in a sign of the deep public misgivings over wading into another foreign conflict, the hearing was interrupted several times by protesters.
As Kerry entered the packed room, a man in a pink shirt yelled "say no to war in Syria" adding: "We cannot afford to have another war, we need health care."
Two polls released Tuesday showed strong opposition to a US military intervention in the crisis. Some 48 percent of Americans told a Pew Research Center survey that they opposed "conducting military air strikes" with only 29 percent in favor.
A poll by the Washington Post-ABC found a similar margin of nearly six in 10 Americans opposed to missile strikes.
The Democratic chairman of the Senate committee, Robert Menendez, said: "There are risks to action but the consequences of inaction are greater and graver still."
But influential Republican Senator John McCain lambasted the administration for delaying its response for so long, before now signalling its intent.
"You tell the enemy you're going to attack them, they're obviously going to disperse and try to make it harder," he said.
And he expressed misgivings about the measure before the Congress, saying: "If it's the wrong kind of resolution, it can do just as much damage."
The Republican-controlled House, which will hear from top administration officials on Wednesday, is seen as the tougher sell for Obama.
Obama said the August 21 attack, which Washington says involved the use of sarin, posed a serious national security threat to the United States and its allies.
"As a consequence, Assad and Syria needs to be held accountable," he said, while assuring Americans he would not use ground troops.
Hagel insisted "we have made clear that we are not seeking to resolve the underlying conflict in Syria through direct military force."
Kerry added that the aim of any strikes would be to degrade Assad's military capabilities.
But he seemed to indicate that the administration would like to preserve the option of sending in troops "in the event Syria imploded, for instance, or in the event there was a threat of a chemical weapons cache falling into the hands" of Al-Qaeda-linked fighters.
For his part, a defiant Assad warned in an interview with Western media released Monday that strikes of any kind could set off a wider Middle East conflict.
"Everyone will lose control of the situation once the powder keg explodes. Chaos and extremism will spread. There is a risk of regional war," Assad told French newspaper Le Figaro.
UN leader Ban Ki-moon also warned that a western military strike could make things worse.
"We must consider the impact of any punitive measure on efforts to prevent further bloodshed," Ban said.
More than 100,000 people have died since the rebellion to oust the Syrian leader erupted in March 2011.
The UN refugee agency Tuesday revealed that some two million Syrians have now fled, in a tide of humanity which is straining resources in neighboring countries. Millions more have been displaced inside Syria.
Antonio Guterres, the United Nations High Commissioner for Refugees, described the figures as a "disgraceful humanitarian calamity with suffering and displacement unparalleled in recent history."