Indianapolis Homeland Security Director Gary Coons made the announcement after meeting with residents of the subdivision where the Nov. 10 blast occurred and shortly after funerals were held for the two victims, who lived next door to the house where investigators believe the explosion originated.
"We are turning this into a criminal homicide investigation," Coons said, marking the first time investigators have called the case criminal.
Search warrants are being executed and official are looking for a white van that was seen in the subdivision on the day of the blast, Marion County Prosecutor Terry Curry said. Authorities are offering at least a $10,000 reward.
Curry said the investigation is aimed at "determining if there are individuals who may be responsible for this explosion and fire."
Neither he nor Coons took questions or indicated if they had any suspects. No arrests have been made.
Officials have said they believe natural gas was involved in the explosion, which destroyed five homes and left dozens damaged, some heavily. Damage has been estimated at $4.4 million.
Investigators have been focusing on appliances as they search for a cause of the explosion.
Hundreds of people attended the funerals earlier Monday for the couple killed in the explosion, 34-year-old John Dion Longworth and 36-year-old Jennifer Longworth. She was a teacher remembered for knitting gifts for her students, while her husband, an electronics expert, was known as a gardener and nature lover.
Indianapolis Mayor Greg Ballard spoke at the news conference and said he went to the Longworths' funeral and had a hard time coming to peace with what had happened.
"There is a search for truth and there is a search for justice," Ballard said.
The couple lived next door to the house where investigators are focusing. The co-owner of that house, John Shirley, told The Associated Press he had received a text message from his daughter recently saying the furnace in the home, which she shares with her mother and her mother's boyfriend, had gone out.
Shirley's ex-wife, Monserrate Shirley, said her boyfriend, Mark Leonard, had replaced the thermostat recently and the furnace had resumed working.
The couple was away at a casino at the time of the blast. The daughter was staying with a friend, and the family's cat was being boarded.
Monserrate Shirley's attorney, Randall Cable, declined comment on the announcement Monday evening.
Associated Press writer Ken Kusmer contributed to this report from Indianapolis.