Investigators believe the blast on Monday was caused by natural gas, said Bureau of Alcohol, Tobacco, Firearms and Explosives spokeswoman Sara Abel, who was briefed by local police.
Two people were in serious condition and the rest had minor injuries, authorities said at a news conference.
Medics also treated four more people on the scene but did not take them to a hospital, said Desiree Partain of MedStar, which provides ambulance and emergency medical services in Fort Worth.
The Sandman Signature hotel is in a busy area of downtown about one block from the Fort Worth Convention Center. Footage from news helicopters showed firefighters picking their way through the piles of drywall, shattered glass and mangled metal that coated the street outside the hotel. Authorities urged people to avoid the area.
"There is a smell of gas in the area and there are windows and things that were blown outside of the structure," said Craig Trojacek, a spokesman for the Fort Worth Fire Department.
Video posted to social media showed a man sitting on a street corner across from the explosion site and holding a woman at his chest. The man appeared to have blood on his forehead, and a medical technician knelt in front of him to tend to his wounds.
A grey haze covered normally busy streets of downtown Fort Worth as firefighters walked through layers of debris. Remnants of the building lay scattered across the street and over parked vehicles, and gaping holes could be seen on the ground.
According to the hotel website, the Sandman Signature Fort Worth Downtown Hotel has 245 rooms and was built in 1920.