A California Highway Patrol officer made a traffic stop just after 2:30 Tuesday afternoon on I5 and Panoche Road.
The officer became suspicious and his K9 searched the vehicle.
About 15 pounds of meth were found in the trunk and cocaine was found on the passenger.
25-year-old Eduardo Castaneda-Reymundo, and 40-year-old Juan Salas-Ponce, both from Washington State, were arrested.
They've been booked in the Fresno County Jail on several felony charges.