The explosion occurred on St. Louis Road in Jefferson City early Saturday morning at 2:44 a.m., according to a press release from Jefferson City Fire.
The cause of the explosion is still under investigation, officials said.
Emergency responders said of the six individuals injured in the blast, two were transported to Jefferson City Airport and flown to University Hospital in Columbia, Missouri.
The remaining four people were transported by ground to University Hospital.
Three of the victims are listed in critical condition and received critical life support, Cole County EMS Chief Eric Hoy told ABC News' Missouri affiliate KMIZ.
The other three have moderate injuries and are stable, the outlet reported.
Photos released by officials show the explosion left the home almost completely leveled, with responders saying they discovered the six individuals among the debris upon arrival.
"Rescue operations were particularly challenging due to the extensive structural collapse and significant debris," Jefferson City Fire said in the release.
"The team had to carefully tunnel through layers of debris to reach the final occupant, who required intensive extrication," officials added.
All six of the individuals were safely removed from the residence by 5:52 a.m.
Additionally, fire officials said in the release that two pets were rescued from the collapsed home and are now in the care of animal control.
ABC News' Maci Smith contributed to this report.