Much of our understanding of the response of savanna systems to fire disturbance relies on observations derived from manipulative fire plot studies. Equivocal findings from both recent Australian and African savanna fire plot assessments have significant implications for informing conservation management and reliable estimation of biomass stocks and dynamics. Influential northern Australian replicated fire plot studies include the 24-year plot-scale Munmarlary and the five-year catchment-scale Kapalga, mesic savanna (> 1000 mm/yr of rainfall) experiments in present-day Kakadu National Park. At Munmarlary, under low-to-moderate-intensity fire treatments, woody vegetation dominated by mature eucalypts was found to be structurally stable. At Kapalga, substantial declines in woody biomass were observed under more intense fire treatments, and modeling assessments implicate early-season fires as having adverse effects on longer-term tree recruitment. Given these contrasting perspectives, here we take advantage of a landscape-scale fire response monitoring program established on three major northern Australian conservation reserves (Kakadu, Litchfield, and Nitmiluk National Parks). Using statistical modeling we assess the decadal effects of ambient fire regime parameters (fire frequency, severity, seasonality, time since fire) on 32 vegetation structure components and abundance of 21 tree and 16 grass species from 122 monitoring plots. Over the study period the mean annual frequency of burning of plots was 0.53, comprising mostly early-dry-season, low-severity fires. Structural and species responses were variable but often substantial, notably resulting in stem recruitment and declines in juveniles, but only weakly explained by fire regime and habitat variables. Modeling of these observations under three realistic scenarios (increased fire severity under projected worsening climate change; modest and significant reductions in fire frequency to meet conservation criteria) indicates that all scenarios have positive and negative structural implications. Effecting significant regional fire regime change (e.g., reduction in frequency and size of severe fires) is demonstrably feasible, but it incurs risks and potentially some undesirable structural consequences. Given recent Australian and African experience, the generality and application of landscape-scale implications derived from manipulative fire assessments (including variable grazing and browsing regimes) in savanna require more critical assessment.