"The civilians were boarding small boats on the northern bank of the Euphrates River to flee southern neighbourhoods of Raqa," said Observatory head Rami Abdel Rahman yesterday.
He said women and children were among the dead but he could not immediately give a specific number.
Thousands of civilians have fled the northern city as a seven-month offensive by the Syrian Democratic Forces (SDF), an Arab-Kurdish alliance, closes in.
The SDF is now several kilometres from Raqa's east, west, and north, and has sealed off routes into the city from those three fronts.
Russian aircraft have also carried out bombing raids against IS convoys fleeing the city.
According to the Britain-based Observatory, the latest coalition raid took place on yesterday morning.
"The toll may continue to rise as some of the wounded are in critical condition," the monitor said.
The activist collective Raqa is Being Slaughtered Silently also reported the strike, saying it hit people "waiting near the river and others on boats (who) were trying to cross."
It said civilians had been escaping Raqa by crossing the Euphrates River via boat, after the two main bridges leading out of the city were destroyed.
The US military has said coalition air strikes in Iraq and Syria had "unintentionally" killed 484 civilians, but observers say the number is much higher.
The Observatory has given a toll of around 1,500 civilians in Syria alone since the coalition began striking there on September 23, 2014.
The monitor recorded the coalition's deadliest month for Syrian civilians between April 23 and May 23, with 225 civilians killed.
Reports of civilian casualties in the air campaign have swelled in recent weeks.
The president has "directed a tactical shift from shoving ISIS out of safe locations in an attrition fight to surrounding the enemy in their strongholds so we can annihilate ISIS", Mattis said, using an acronym for IS.
But the Pentagon has denied that its rules of engagement have changed and insists that the coalition continues to strike only "military-appropriate targets".
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