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Abstract Global change is shifting disturbance regimes that may rapidly change ecosystems, sometimes causing ecosystems to shift between states. Interactions between disturbances such as fire and disease could have especially severe effects, but experimental tests of multi‐decadal changes in disturbance regimes are rare. Here, we surveyed vegetation for 35 years in a 54‐year fire frequency experiment in a temperate oak savanna–forest ecotone that experienced a recent outbreak of oak wilt. Different fire regimes determined whether plots were savanna or forest by regulating tree abundance (r² = 0.70), but disease rapidly reversed the effect of fire exclusion, increasing mortality by 765% in unburned forests, but causing relatively minor changes in frequently burned savannas. Model simulations demonstrated that disease caused unburned forests to transition towards a unique woodland that was prone to transition to savanna if fire was reintroduced. Consequently, disease–fire interactions could shift ecosystem resilience and biome boundaries as pathogen distributions change.