Tree regeneration is a critical mechanism of forest resilience to stand-replacing wildfire (i.e., where fire results in >90 % tree mortality), and post-fire regeneration is a concern worldwide as the climate becomes warmer. Although post-fire tree regeneration has been relatively well-studied in fire-prone forests across western North America, it is less understood in fire regimes characterized by large patches of stand-replacing fire at long intervals, such as the nominally infrequent, high-severity fire regimes of the western Cascades of Washington and northern Oregon, USA (northwestern Cascadia) where some of world’s highest-biomass forests reside. Recent wildfire activity (2015–2020) in northwestern Cascadia provides a unique opportunity to build understanding of the mechanisms underpinning forest resilience to fire, with implications for forest management and the myriad socio-ecological values associated with these landscapes. Here, we asked: how is post-fire conifer regeneration across northwestern Cascadia affected by pre-fire stand age, burn-patch size, and topo-climatic conditions? We established 39 1-ha long-term monitoring plots across four recent wildfires in northwestern Cascadia to measure post-fire conifer abundance and species composition. We used generalized linear models to test how rates of conifer regeneration (seedlings ha−1 yr−1 of all heights) and establishment (seedlings ha−1 yr−1 with heights >10 cm) respond to differences in pre-fire stand age/seral stage (young, mid-seral, late-seral), distance to the nearest live seed source, and post-fire topo-climate setting. In general, initial post-fire seedling densities suggest tree regeneration is abundant following stand-replacing fire in most areas across the region. For example, at 3–5 years post-fire, established seedlings were present in 100 % of plots, and regeneration and establishment levels exceeded state forest practices minimum density thresholds (470 seedlings ha−1) in 82.1 % and 64.1 % of plots, respectively. Post-fire conifer regeneration and tree species richness were greater when pre-fire stand age was older, and was more dominated by shade tolerant species than when pre-fire stand age was younger. Regeneration decreased with farther distances to the nearest live seed source, though seedlings were still moderately abundant at distances as far as 400 m from edges of high-severity patches. Conifer establishment was greater in areas characterized by cooler and wetter macrosite (e.g., greater post-fire precipitation) and microsite (e.g., greater bryophyte ground cover) conditions. By providing information on the drivers and conditions in which land managers can expect natural regeneration to occur or not, our findings are directly relevant to pre- and post-fire forest management objectives under future climate and increased fire activity in systems structured in part by infrequent and severe wildfires.