The wreck at Highway 29 and Cruickshank Road in Kelseyville was reported just before 5 p.m.
The California Highway Patrol said the crash involved a silver Toyota and a white semi truck, with the truck reported to have gone 20 feet down an embankment.
Just before 6:30 p.m., the semi caught fire, with one report from the scene stating that something was popping inside the semi.
A short time later, the CHP reported that Highway 29 was closed from Bottle Rock Road to Main Street in Kelseyville, with traffic routed around the site.
One-way traffic control through the area was implemented at around 7:15 p.m. with the roadway reopened just after 8:30 p.m., as tow trucks worked to remove the semi and trailer, according to the CHP.
Firefighters reported that the incident was terminated shortly after 9 p.m.
Details about injuries and what led to the crash were not immediately available on Tuesday night.
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