Unknown gunmen attacked the White Helmet members at a base in Sarmeen, in the rebel-held province of Idlib.
The motive for the killing remains unknown. The attackers stole two minibuses and walkie-talkies, the group said.
The US state department said it was "saddened and horrified" by the attack.
"These cowardly acts of masked men took the lives of civilian volunteers who work tirelessly as first responders in order to save lives in incredibly dangerous environments," a statement said.
