The discovery was made around 10 a.m. Wednesday. An officer noticed something unusual and called in a canine team to inspect the bus.
Investigators also questioned the driver, who was described only as a 56-year-old man from Mexico.
Officers then ran the bus through an imaging system. They searched the bus and found 110 marijuana packages inside the gas tank, weighing about 1,071 pounds, with a street value of $482,000.
The driver was arrested and transported to the Metropolitan Correctional Center in San Diego.