Fire is becoming a pervasive driver of environmental change in Amazonia and is expected to intensify, given projected reductions in precipitation and forest cover. Understanding of the influence of post-deforestation land cover change on fires in Amazonia is limited, even though fires in cleared lands constitute a threat for ecosystems, agriculture, and human health. We used MODIS satellite data to map burned areas annually between 2001 and 2010. We then combined these maps with land cover and climate information to understand the influence of land cover change in cleared lands and dry-season severity on fire occurrence and spread in a focus area in the Peruvian Amazon. Fire occurrence, quantified as the probability of burning of individual 232-m spatial resolution MODIS pixels, was modeled as a function of the area of land cover types within each pixel, drought severity, and distance to roads. Fire spread, quantified as the number of pixels burned in 3 × 3 pixel windows around each focal burned pixel, was modeled as a function of land cover configuration and area, dry-season severity, and distance to roads. We found that vegetation regrowth and oil palm expansion are significantly correlated with fire occurrence, but that the magnitude and sign of the correlation depend on drought severity, successional stage of regrowing vegetation, and oil palm age. Burning probability increased with the area of nondegraded pastures, fallow, and young oil palm and decreased with larger extents of degraded pastures, secondary forests, and adult oil palm plantations. Drought severity had the strongest influence on fire occurrence, overriding the effectiveness of secondary forests, but not of adult plantations, to reduce fire occurrence in severely dry years. Overall, irregular and scattered land cover patches reduced fire spread but irregular and dispersed fallows and secondary forests increased fire spread during dry years. Results underscore the importance of land cover management for reducing fire proliferation in this landscape. Incentives for promoting natural regeneration and perennial crops in cleared lands might help to reduce fire risk if those areas are protected against burning in early stages of development and during severely dry years.