The crash happened at 3:20 a.m. Sunday, on the 405 Freeway near the 101 Freeway.
Investigators say Timothy Truc lost control of his car, crossed all four lanes on the northbound 405, and hit the divider. His car flipped, caught fire and ended up in the southbound lanes.
The Good Samaritans, identified as Khoren Moughalian and Jason Abraham, found the man unconscious in the driver's seat at the scene of the crash.
One of the men, an off-duty security guard, cut the driver's seat belt to free him, using only a hand knife.
After getting treatment at the hospital, officers arrested Truc on suspicion of driving under the influence.