It happened around 6:30 p.m. along SR-118 at Sand Canyon Road, between Somis and Moorpark.
The Ventura County Fire Department said six Amtrak train cars were involved, all of which stayed on the tracks except one.
The Amtrak Pacific Surfliner was headed south to Los Angeles, carrying 95 passengers and five crewmembers.
The five people sent to the hospital reportedly suffered only minor injuries, authorities said. The driver of the semi-truck driver was also evaluated for injuries but his or her condition remains unknown.
As of Tuesday night, the crash was impacting both train and road traffic in the area. People were urged to drive with caution.