Crews were called around 2:30 am on Thursday to Anna and Church Avenues.
When they arrived, they found flames coming from two trailers filled with tires.
Firefighters had to cut a fence to enter the grounds. The storage yard was filled with old vehicles, boats and car parts.
Officials said burning tires are tough to put out.
"It is a challenge for us. Not only a lot of water, but it puts off a lot of really bad smoke with chemicals, so our firefighters really have to make sure they're on breathing apparatus the whole entire time," said Fresno Fire Battalion Chief Tim Fulmer.
The smoke and flames could be seen along Highway 99.
An investigator is working to determine what caused the fire. No one was hurt.