The two-alarm fire spread to a nearby home where firefighters were on the roof trying to contain the damage.
The incident was reported around 3:30 p.m. on E. Colorado Boulevard near Gladys Avenue.
Aerial footage showed most of the structure reduced to smoldering ash. A gas line continued to emit flames.
Investigators say no one was killed, but they're still trying to determine what caused the incident.
Neighbors reported hearing what sounded like an explosion around the time of the fire.
"I was bringing in the trash barrels and boom," neighbor Tim Price said. "It was instant flames. It just blew out all the windows."
Firefighters arrived to battle the blaze, but they could not save the house.
The flames spread to a neighboring home and caused significant damage. Residents living there were not injured, but the house has been red-tagged.
The owner was not at home when the flames broke out. He returned to find his house reduced to rubble. Authorities are searching for another man believed to be a tenant.
"There is a tenant that is unaccounted for. The landlord, the owner of the home - we have made contact with him, and we'll be doing our best to make contact with the tenant," Monrovia Fire Chief Jeremy Sanchez said.
Arson investigators carefully combed through the charred rubble, trying to determine what caused the fiery explosion. They found no evidence of human remains.