Lewis had been scheduled to face Canadian Kirk Johnson, but Johnson was forced to pull out of the fight when an MRI last week revealed a partially torn left pectoral muscle suffered sparring at his Dallas-Fort Worth training camp.
The 6-7 1/2 Klitschko (32-1, 31 KOs) is the top-rated contender by the WBC and was scheduled to face undefeated Cedric Boswell on the undercard of the Lewis-Johnson bout. Klitschko and Lewis were slated to meet some time later this year.
"This has been a life-long dream of mine to fight Lennox Lewis," Klitschko said. "I am very excited about the opportunity to fight him in Los Angeles and on HBO. It is going to be a great fight."
Lewis (40-2-1, 31 KOs) has not fought since recording a dominating eighth-round knockout of former champion Mike Tyson last June.