Santa Ana wind (SAW) events have great implications for the environment of Southern California, but the cause of their decadal variability has not been fully understood. We show with observational analysis that the Atlantic multi-decadal oscillation (AMO) has a stronger influence than the Pacific decadal oscillation (PDO) in modulating SAW activity through two mechanisms: the Great Basin pressure gradient mechanism, in which a strengthened Great Basin high promotes SAW activity and vice versa through the northeast-southwest pressure gradient across Southern California, and the Pacific jetstream displacement mechanism, in which a strengthened Pacific subtropical high (PSH) prohibits mid-latitude cyclones from traveling toward California, consequently encouraging SAW development and vice versa. While the AMO strengthens or weakens both the Great Basin and PSHs to strongly modulate SAW activity through these two mechanisms, the PDO strengthens one of the highs but weakens the other, causing the two mechanisms to cancel each other, producing little influence on SAW activity. A projection based on the AMO and PDO indicates that the above-average SAW activity observed since the beginning of the 21st century is likely to terminate after 2016, after which Southern California may experience an extended period of below-average SAW activity through