At least five other people were seriously hurt at the Flat Top Little General Store, where little remained except twisted metal and a sign showing the price of gasoline.
The blast was felt at least a mile away at a store selling skiing gear.
"I thought we got struck by lightning. The whole building shook. The power went off," said Ben Monast, manager of the Ski Shop.
Bystanders said there was an odor of gas before the explosion, reports CBS News affiliate WVNS.
Ghent Elementary, which is about a mile away from the school, suffered minor damage in the explosion, adds WVNS.
Authorities suspect the explosion happened in a propane tank just as a fire truck was pulling into the station in response to a reported leak.
A firefighter and a paramedic were among those killed, said Celeste Hinzman, spokeswoman for the state Division of Homeland Security and Emergency Management.
State Fire Marshal Sterling Lewis said an above-ground tank capable of holding 500 pounds of propane was being worked on at the time of the blast.
"It is our initial thought that the fumes entered into the building and had to have an ignition point," Lewis said.
Keli Akers said she was driving to her house about a mile from the gas station Tuesday when she began to smell propane. When she got home, she saw debris falling into her yard.
Akers said her mother "felt a huge jolt" at the time of the blast.
Akers tried to drive to the scene, but she could get no further than a nearby elementary school because roads were closed. The school was also damaged.
"I know people there," she said. "But it's not just the people who work there. Everyone goes there. Anyone could have been there."
The gas station was about 70 miles southeast of Charleston.