Game reserves (GR) in Tanzania have been found to support similar or lower densities of large mammals compared with National parks (NP). But as these areas usually differ considerably not only in regard to management but also to environmental factors, we assessed the relative importance of vegetation cover, species-speciﬁc habitat preferences and legal (trophy hunting) and illegal off-take for observed differences in species-speciﬁc densities. In the Katavi ecosystem, open habitats were characteristic elements of Katavi NP, while Rukwa GR was dominated by miombo forest. In an inter-speciﬁc comparison, density differences were moderately correlated with preferences for open habitats, and with estimates of combined legal and illegal off-take but not with one of these separately. In a multiple linear regression, open habitat preference was found to explain 39.6% of the density differences between the two protected areas. This analysis suggests that the broad-scale pattern of most species’ distributions is governed by differing vegetation cover but that several species are over exploited by illegal (elephant, giraffe, buffalo, bush pig, warthog) or combined off-take (hippopotamus, eland, waterbuck), thus emphasizing the need for quota readjustments and a more efﬁcient anti-poaching control.