The fire erupted north of State Route 134 near Chevy Chase Canyon and has burned close to structures.
Los Angeles Fire Department spokesman Erik Scott says the blaze was reported just after 2 p.m. Friday.
Four helicopters are responding to the scene.
Low visibility from the smoke has prompted closure of the Glendale Freeway between State Route 134 and Interstate 210, causing traffic to back up for miles.
Immediate evacuations are underway in the vicinity.
Glendale Community College has canceled its Friday night classes.