The fire has already destroyed five homes, damage another dozen and is threatening 1,000 more, Cal Fire announced on Twitter.
The Lilac Fire has charred approximately 500 acres of land.
State Route 76 is closed in both directions.
Thick white smoke could be seen by neighbors in the southeastern part of San Diego County.
Mandatory evacuations were ordered in the area of West Lilac Road and Sullivan Middle School.
A brush fire is burning near Interstate 15 and SR-76 in North County San Diego, according to the California Highway Patrol.
Temporary shelters have been set up at Fallbrook High School, the East Valley Community Center in Escondido, Pechanga Casino and Pala Casino, according to CAL Fire.
There is no active wildfire working in San Diego County at this time.
The cause of the blaze - which broke out amid a National Weather Service "red flag" wildfire warning slated to expire Sunday night - was not immediately clear.