The increasing human pressure has threatened wildlife conservation, even in protected areas. However, findings reporting the effects of human on wildlife conservation are not consistent. This study aimed to investigate the effect of human disturbance on the distribution and abundance of mammals in Abijata-Shalla Lakes National Park considering the consumptive and non-consumptive modes of human activities. The study was conducted from September 2017 to February 2018 in three selected sites, which were stratified based on human disturbance as nature conserved areas, sites engaged in consumptive livelihood, and ecotourism sites. Data were collected using a line transect method. The distribution and abundance data were analyzed using Chi-square tests and one-way ANOVA, respectively. There was a significant difference on the distribution of target wild animals in the selected sites; greater kudu (P < 0.001), warthog (P < 0.01), and bohor reedbuck (P = 0.03) were highest in the “nature conserved” site. Human disturbance also significantly affected the abundance of warthog (P = 0.028), greater kudu (P < 0.001), and bohor reedbuck (P = 0.024). Greater kudu distribution was limited in nature conserved site. However, Warthog and Bohor Reedbuck were distributed in all sampling sites; nature conserved sites hold the highest population abundance. The results indicate that consumptive local livelihood and ecotourism disturbances adversely affected the distribution and abundance of mammals relative to the nature reserved site. However, ecotourism favored some mammal species from the consumptive local people’s livelihood activities. Thus, to reduce the impact of human disturbances on wildlife conservation, monitoring and controlling the level of human disturbance is urgent. Sustainable practices such as community engagement, awareness creation and alternative livelihood options should be proposed.