The crash was reported around 4 a.m. near Alvarado Street, according to the California Highway Patrol. Officials said the driver of a red Prius was traveling northbound in southbound lanes.
"Moments later, the vehicle then collided with a Honda vehicle traveling southbound... it was side-swiped. That allowed that wrong-way vehicle continue and then went head-on into a pickup truck," said CHP Officer Roberto Gomez.
The Prius and at least one other vehicle involved in the collision were engulfed in flames after the impact. The CHP said the wrong-way driver was pronounced dead at the scene.
At least two others were injured and transported to the hospital.
"It was just a chain of events that unfortunately we had one person lose their life because of it," Gomez said.
The debris from the crash flew onto the opposite side of freeway, causing more accidents on northbound lanes as passing drivers tried to get a look at what was happening.
Gomez had this message for anyone passing by a major accident: "Please put all the distractions away. Pay attention to what's ahead, and then we can all get there on time, safely."
The CHP is still investigating the incident and could not say if the person who died was driving under the influence.
The collision initially prompted the closure of all southbound lanes, but the freeway fully reopened around 8:30 a.m.