The drill began as scheduled at 10:19 a.m. at locations including the Natural History Museum in Exposition Park.
"They told me to drop and go under a table and hold on," said a boy who was among a group of students visiting the museum.
As more time passes since California's last major earthquake, the more the ShakeOut drill is seen as necessary.
"Clearly we're overdue," said Jeff Primes of Ready America. "And it's not a question of if we're going to have the next big earthquake, it's a question of when it will be."
Survival kits - stocked with water, food and a radio, among other items - can be crucial after a major temblor.
Experts also recommend having an emergency plan for families.
"People need to prepare now," said Veronica Verde, a spokeswoman for FEMA. "It's something that's going to be happening soon. It's not if, it's when it's going to happen. Disasters don't plan ahead but you can."