Kamloops RCMP said there is little chance of finding the driver alive, and the B.C. Coroners Service has been notified of the incident.
The semi truck was found Tuesday morning completely submerged, just off a curvy portion of the Trans Canada directly to the east of Little River Boatworld, and about 14 kilometres from Chase. The driver's body has yet to be located.
By the time police arrived, the trailer had floated about a kilometre away, toward Chase.
Cpl. Mark Skotnicki said no one knows yet what happened on the stretch of highway.
"This was an un-witnessed event, to our knowledge at this time."
"[We] just got a call from a driver who spotted what looked like debris in the lake."
Police are now looking over the accident scene for clues as to why the truck left the highway, but say the driver most likely failed to make it around an S-curve.
DriveBC reported that the highway would be closed in both directions at the crash scene, with no local detour, from approximately 3 to 5 p.m. PT while crews recover the truck.