Pseudo-nitzschia species with the ability to produce the neurotoxin domoic acid (DA) are the main cause of harmful algal blooms (HABs) along the U.S. West Coast, with major impacts on ecosystems, fisheries, and human health. While most Pseudo-nitzschia (PN) HAB studies to date have focused on their characteristics at specific sites, few cross-regional comparisons exist, and mechanistic understanding of large-scale HAB drivers remains incomplete. To close these gaps, we compiled a nearly 20-year time series of in situ particulate DA and environmental observations to characterize similarities and differences in PN HAB drivers along the California coast. We focus on three DA hotspots with the greatest data density: Monterey Bay, the Santa Barbara Channel, and the San Pedro Channel. Coastwise, DA outbreaks are strongly correlated with upwelling, chlorophyll-a, and silicic acid limitation relative to other nutrients. Clear differences also exist across the three regions, with contrasting responses to climate regimes across a north to south gradient. In Monterey Bay, PN HAB frequency and intensity increase under relatively nutrient-poor conditions during anomalously low upwelling intensities. In contrast, in the Santa Barbara and San Pedro Channels, PN HABs are favored under cold, nitrogen-rich conditions during more intense upwelling. These emerging patterns provide insights on ecological drivers of PN HABs that are consistent across regions and support the development of predictive capabilities for DA outbreaks along the California coast and beyond.