"The biggest challenge we have in Syria, the reason why this keeps happening again and again is because there is no accountability and no justice," Salil Shetty told AFP.
"It's one thing to have some air strikes by the US on a one-off basis, but it's not going to address this problem," he said.
Washington last week launched its first direct military action against President Bashar al-Assad's regime, after accusing the Syrian leader of using chemical weapons on a rebel-held town, killing dozens of people.
"It has to be part of a much larger concerted effort to ensure accountability; you can't just have a knee-jerk reaction," he said, urging a UN investigation.
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Washington launched its attack on the Shayrat air base in central Syria's Homs province after the UN Security Council failed to take action, with Assad ally Russia opposing a draft resolution setting the terms for a swift enquiry.
Moscow has regularly blocked Security Council resolutions it considers unfair to Damascus, and Shetty slammed all five permanent members of the council for playing "politics".
"Instead of taking care of global peace and global interests, they play politics."
He also criticised US President Donald Trump's attempts to bar Syrian refugees, saying they stood "in complete contradiction" to the concern he expressed for civilians in the wake of the Khan Sheikhun attack.
More than 320,000 people have been killed in Syria since the conflict began in March 2011 with anti-government protests.
More than five million Syrians have become refugees, with most finding safety in neighbouring countries, including Lebanon.
Shetty praised Lebanon for its welcome of refugees, and said Amnesty would continue pressuring the international community to provide greater assistance to the government to absorb spiralling costs.
But he also warned against "a growing tide of xenophobic talk" in the country.
"It is important for the leaders of this country to send a clear message...That is beyond the pale, that is not acceptable," he said.
"The Lebanese have not been xenophobic: you've done so much and this is a good time for you to reign in those kinds of tendencies.