The blaze started at around 12:30 a.m. at a home in an unincorporated part of the county known as Reche Canyon, north of Moreno Valley.
The flames took about three hours to knock down, mostly because the closest water source is about a mile away.
Authorities said it was a fairly extensive grow operation- it took up a large portion of the 4,000-square-foot home.
"We don't know the exact number of plants inside the residence due to the fire damage," said Sgt. Joe Borja from Riverside County Sheriff's Department. "What I can tell you is that it covered three-quarters of the first floor of the residence so it was a substantial amount."
Firefighters said no one was inside the home and no injuries were reported. They found a dog at the house, but the animal is OK. It was taken away by Animal Control. The dog's tags indicated the owner is from the Los Angeles area.
The fire department removed about a dozen of the plants so the sheriff's department could investigate the matter. But the vast majority of marijuana was wiped out in the fire.
Investigators are still searching for the individuals responsible for the operation. Detectives said there are a number of possibilities.
"It could have been squatters or what have you," said Borja. "The residence was abandoned for some time, so we're still trying to determine who's responsible for the marijuana inside the residence."
The cause of the fire is also under investigation.