Australian mammals have exhibited exceptionally high rates of decline since European settlement 230 years ago with much focus on small mammals in northern tropical savannas. In these systems, little scientific attention has been given to the suite of grazing macropods, family Macropodidae, (common wallaroo (Osphranter robustus), antilopine wallaroo (O. antilopinus) and agile wallaby (Notamacropus agilis)). These species may be impacted by feral herbivores and contemporary fire regimes, two threats linked to small mammal declines. A multi-scale approach using aerial surveys, road surveys and camera trapping was utilised to determine the effects of feral cattle and fire on the distribution and abundance of large macropods in the North Kimberley bioregion. Feral cattle density and biomass exceeded that of macropods regardless of survey technique. Density estimates for cattle were up to 125 times higher (0.3–10.0 km−2) than estimates for macropods (0.08–0.49 km−2). Cattle biomass, based on the aerial survey estimates (corrected for perception bias), were 15 and 95 times higher than macropods for infertile (279 vs. 19 kg km−2) and fertile savannas (518 vs. 5 kg km−2), respectively. Proximity to the nearest pastoral station was a significant predictor of the aerial sightings of feral cattle (P ≤ 0.05). Abundance and foraging activity of cattle were positively associated (P ≤ 0.05) with recently burnt areas. In contrast, camera trapping showed agile wallaby and wallaroo occurrence and foraging were associated with longer unburnt areas (P ≤ 0.05). Agile wallaby and wallaroo were negatively associated with cattle (P ≤ 0.05) and showed substantial diurnal and seasonal separation consistent with an antagonistic interspecific interaction. Results also suggest that the agile wallaby is the primary prey of the dingo, not wallaroo. Collectively, this study suggests that recent landscape changes such as altered fire regimes and introduced herbivores have negatively impacted large grazing macropod species.