The crash occurred near the Western Avenue interchange at 9:53 p.m.
Ryan Daniel Dylewski of Lancaster was pronounced dead at the scene.
CHP says the victim's 2011 Suzuki rear-ended a 2000 Nissan and was ejected from the motorcycle. The Suzuki was then hit by a 2004 Yamaha driven by a 38-year-old woman from Lancaster. She suffered moderate injuries in the crash.
Dylewski was then fatally struck by an unknown vehicle, and then a 2004 Saturn driven by a 48-year-old man from Palmdale.
The driver of the Nissan was arrested at the crash. Further details were not released.
Three southbound lanes of the freeway were closed for several hours, but have since been reopened.