The crash was reported at about 6:50 a.m. on Mount Hermon Road east of East Zayante Road, the dispatcher said.
California Department of Fish and Game spokeswoman Carol Singleton said that between 40 to 80 gallons of fuel had spilled into a creek and onto the roadway. As of 11:30 a.m., the big-rig was still leaking, she said.
The road will remain closed this morning as Caltrans and the Department of Fish and Game crews work to clean up the spill.
One minor injury was reported.