The fire was reported at 1:30 p.m. at 500 W. Main St., and about 50 firefighters from various departments responded.
The cause of the fire remains under investigation.
At least four apartments sustained significant smoke and fire damage, said Stacy Beard, spokeswoman for Clayton.
A mother and her son son were treated for smoke inhalation, and the boy's father later reported that he was experiencing health issues as well, Beard said.
The American Red Cross was assisting at least 11 people displaced by the fire, including two families and a couple celebrating their 15th anniversary.
Firefighting operations closed Main Street between Robertson and Moore streets for almost four hours.
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