Fresno Fire tells Action News that the facility near Nielson and Teilman was vacant.
After serving as the morgue, it was briefly used as an animal shelter.
The first call about the fire came in at 7:20am on Tuesday.
When the first crew arrived, they saw heavy smoke and flames and said the fire was already spreading from the first floor to the second floor.
Firefighters decided to take a defensive stance, and ladder trucks were quickly set up to begin pouring water on the fire from above to douse the flames.
"Due to the structural integrity of the building, we've also had multiple fires here in the past. the concern was a collapse -- so we took a defensive approach," said Josh Sellers with the Fresno Fire Department.
As of 8:30 am, there were 36 firefighters on scene and many are expected to remain there for several hours.
This is just the latest of many fires in the building over the years after it was left vacant.
Supervisor Nathan Magisg confirmed to Action News that the county still owned the building. It is expected to be a total loss after this fire.
"One of the challenges that we've had as a county -- we've had that property fenced off -- there have been people who have gone in and vandalized that particular building," said Magsig.
The empty structure was condemened years ago. Now the charred property could be on the county's chopping block.
"Right now, the board of supervisors actually initiated a process where we are looking at all lands throughout Fresno county that are excess property that we are going to be selling off, this is probably going to be one of those sites that we are going to be selling at some point in the future," said Magsig.
Pershing Continuation and Pathway Community School are across the street from the building so Central Unified officials are sending students home for the day. Administrators confirm to Action News students are cleared to return to school Tuesday.
The fire can be seen from many parts of Fresno, including along highways 99 and 180 in Downtown.
For news updates, follow Brianna Willis on Facebook, Twitter and Instagram.