The small- and medium-level quakes were felt from San Diego and Orange County in California east into Arizona, and swamped the temblor-measuring resources of the US Geological Survey (USGS).
The quakes began around 12:16 pm (2016 GMT) with a magnitude 4 temblor 16 miles (26 km) north of El Centro, California, and lasted more than two hours. The biggest shakes included a magnitude 5.4 at 13:57, with the same epicenter.
The so-called "seismic swarm" is a relatively rare occurrence.
"We haven't seen one of these since the 1970s, and there was another one back in the 1930s," said USGS seismologist Lucy Jones.
"Our system is choking on so many earthquakes."
Buildings were evacuated in Brawley, 115 miles east-northeast of San Diego. "It's pretty bad, we had to evacuate the hotel just for safety," said Rowena Rapoza, office manager at the Best Western Hotel there.