Most of the victims were killed by airstrikes on at least five days of strikes carried out at night across five neighborhoods of the rebel-held area, a UN spokesman said.
About 40 people were injured. Among the dead were many women and children.
The mayor of Douma, Bashar Ja’afari, said at least 100 people had been killed, the state-run Syrian Arab News Agency reported.
UNICEF emergency response coordinator Jan Egeland called the attack a war crime.
Witnesses have described hearing a series of explosions at 7:22 p.m. The missiles struck, raining down fire on the rebel enclave, killing people in their beds, according to the Syrian Observatory for Human Rights. The U.S. State Department condemned the strikes.
“This is an attack that is directly against the women and children of Syria,” State Department spokeswoman Heather Nauert said at a briefing. “This is a war crime.”
The US-led coalition has previously targeted suspected chemical weapons facilities and military bases that were linked to a suspected chemical weapons attack in April 2017. That attack killed dozens of people, including many children.
According to a UN report on the attack, the Syrian government denies its aircraft had taken off from an airbase prior to the April 4, 2017, strike.
But the US military maintains its aircraft took off from another base just outside of the war-torn country’s capital, and conducted strikes on the airbase after determining a Syrian air force jet dropped an aerial bomb containing chemicals on the town of Khan Sheikhoun, where more than 70 people were killed and hundreds more were injured.
CNN has previously reported that US officials believe the Syrian military used chlorine as a chemical weapon, but not nerve agent sarin, in the attack.
President Donald Trump said at the time that the US would not stand by if Syria used chemical weapons again, and last August, US missiles launched from ships in the Mediterranean struck a Syrian military airbase that was used to coordinate the bombing campaign in Douma.
In March, US Defense Secretary James Mattis said the strike had caused “significant damage” to the base’s air defenses.
The administration, before the strikes, had said the US was prepared to hit yet another Syrian airfield should evidence emerge of another chemical weapons attack.
But on March 31, Tillerson told a Senate committee the US would be “very careful” with any US military strike in response to the Douma attack.
At the time, he said any US military response would have to strike a “wider, wider area, so that the intent is very clear.”