The suspect reportedly got out of a vehicle on the highway's northbound lanes and began shooting. Three CHP officers responded to the scene just after 5:30 p.m. and engaged with the armed man, police said.
All three fired their weapons, killing him.
The incident was initially reported as a traffic collision involving two vehicles on the highway, CHP officials said.
Northbound Highway 101 was closed around 6:15 p.m. Friday as officers investigated and worked to clear the scene. the CHP tweeted that the lanes reopened around 12:45 a.m. on Saturday.
Following protocol in officer-involved shootings, three agencies are involved independently in the investigation of the incident, police said.
Inspectors with the San Mateo County District Attorney's Office will investigate the legality of the officers' actions. San Mateo police will investigate the alleged criminal aspects of the suspect. The CHP will also conduct an administrative investigation of the officers' actions, according to police.
All three agencies were at the scene for several hours and the investigation is ongoing.
No CHP officers were injured in the fatal shooting.
The California Highway Patrol issued a Sig-alert for all the highway's northbound lanes, just south of Highway 92. The incident caused a massive backup in the area and drivers in the San Mateo area have been asked to avoid the highway.
Adding to the traffic woes in San Mateo County, northbound Highway 101 in Menlo Park was briefly closed at Marsh Road due to a multi-vehicle collision, Menlo Park police officials said at 7:15 p.m. The highway in Menlo Park has since reopened.
Stay with ABC7 News for more details on this developing story.
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ABC7 News reporter Cornell Barnard contributed to this report.