The crash was reported just after 5 a.m. where the highway crosses over 16th Street, near where Interstate Highway 80 meets Highway 101, California Highway Patrol Officer Tony Tam said.
The crash involved the big-rig and three other vehicles, Tam said. Fuel from the truck leaked onto the roadway, sparking a fire that spread to the truck's cab, gutting it, Tam said.
Two people were injured -- the truck driver and a female who was in one of the other vehicles and complained of minor pain, Tam said.
The two left lanes of the highway were reopened shortly before 11:30 a.m., Bartlett said.
He said the two right lanes will remain closed until crews repair a guardrail on the side of the road. There was no estimate for when the highway would fully reopen, he said.
Southbound U.S. Highway 101 in San Francisco will remain shut down until about noon today because of a fiery early morning big-rig crash that injured two people. The crash was reported just after 5 a.m. where the freeway crosses over 16th Street, near where Interstate Highway 80 meets Highway 101, CHP Officer Tony Tam said.
The crash prompted the closure of several on-ramps to Highway 101, including at Seventh and 10th streets, backing up traffic throughout the city's South of Market neighborhood.
Drivers were being advised to take Interstate Highway 280 as an alternate route.
Live traffic maps: