The fatalities included a 55-year-old woman found in the basement of the destroyed home and an 8-year-old boy also pulled from the rubble, Carlinville Police Chief David Haley said at a news conference.
A cause of the explosion was not immediately known, but crews from the local utility were on the scene and a spokesman said they were investigating whether there was a gas leak. The explosion occurred at about 7:30 a.m. in this community 60 miles northeast of St. Louis.
Haley said a 27-year-old man sustained burns over 30 percent of his body, and a 15-year-old boy was severely burned. Both victims were flown to Memorial Hospital's burn center in Springfield, about 55 miles away.
An elderly woman from a neighboring home was also taken to a hospital with cuts, officials said.
The names of the dead and injured were not immediately released.
Leigh Morris, a spokesman for St. Louis-based Ameren Corp., the supplier of natural gas and electrical service through its AmerenIP subsidiary, said the utility had crews on the scene and investigating, along with the state fire marshal.
"Was it caused by a gas leak? I don't know," Morris said. "That's what they're working on right now."
The blast, which heavily damaged a home neighboring the residence that was destroyed, scattered debris over a four-block area and blew out numerous windows, Mayor Robert Schwab said. Haley said a total of at least 15 homes suffered some damage.
Matt Steward, who lives two blocks from the explosion site, said he was watching television with his daughter when he heard the blast.
"The power flickered, and then the huge explosion. It rattled everything in the house," he said.
Steward's home wasn't damaged, but the window was blown out of his pawn shop.
Morris said about 220 AmerenIP customers in Carlinville lost their electrical power about 7:40 a.m. when an Ameren employee cut the service after the explosion downed a primary distribution line, posing a possible threat to emergency responders.
"We had the choice: Cut the power or endanger the lives of the firemen and other people who had to be on the scene. We elected safety first — that's always our position," Morris said.
Morris could not immediately say when power would be restored.
Schwab said people displaced by the explosion are being offered shelter in a cooling center set up at a local college.