The cruise line's Mariner of the Seas, a 3,100-passenger vessel, will end up in its new home base of Galveston, Texas.
Norwegian Cruise Lines will pull its Norwegian Star out of port in May. The 2,348-passenger ship will end up in Tampa, Fla.
The two ships combined carried nearly half of the Port of Los Angeles' passengers in 2009.
Carnival Cruise Lines' Spirit, which has been docked in Los Angeles and San Diego, is also leaving. Beginning in 2012, it will be shipping out of Australia.
The absence of the ships will be felt in Los Angeles. Every cruise ship that goes into port in Los Angeles feeds about $1 million into the local economy.