Holtville is a city in Imperial County, California. Holtville is located 10.5 miles (17 km) east of El Centro. The population was 5,939 at the 2010 census, up from 5,612 in 2000.

U.S. Route 80 (US 80) was a U.S. highway in California that continued east across the country to Georgia. The western terminus of US 80 was in San Diego, California, and it continued east through the city on several different alignments through the years. The highway went through the Cuyamaca Mountains, encountering many switchbacks, before descending to El Centro. After passing through the sand dunes, the highway crossed the Colorado River into Yuma, Arizona.