Human–wildlife conflict is a challenging issue that requires the attention of conservationists worldwide. Habitat fragmentation and encroachment reduce the abundance of prey species, and an increase in the number of predators leads to a higher risk of conflict with large cats such as leopards, jeopardizing conservation efforts. This study explored the spatio-temporal pattern of the human–leopard conflict in Bardia National Park, Nepal, from 2000 to 2020. To analyze the conflict with leopards, we used data (compensation cases filed in the park) from the buffer zone management office, the National Trust for Nature Conservation (NTNC), and the Department of National Park and Wildlife Conservation (DNPWC). Leopard attacks on livestock are increasing exponentially, with 3335 livestock killed in 2652 attacks occurring during the study period. Although livestock depredation by leopards occurred all over the park, the southern cluster has most documented livestock damage (64.01%). The eastern and northern clusters reported fluctuating and dispersed predation events, respectively. Our spatial analysis indicated no effect of topography (slope) on livestock depredation by leopards. We recorded the highest number of leopard attacks and predation during the dry winter season when the nights are longer and livestock remain in their sheds. This carnivore mostly limited its prey to small-sized livestock (95.77%) such as goats, sheep, and pigs, whereas attacks on large-sized (cow and buffalo) livestock were least frequent. Among small-sized livestock, goats are the most predated (66.92%), followed by pigs (20.30%), in all seasons. The escalating human–leopard conflict in BNP is thus a severe threat to conservation efforts as the park has already invested a substantial amount of money (approx. USD 80,000) compensating for livestock lost in leopard attacks over the last two decades. Improving habitat conditions to reduce competition inside the park, developing an insurance scheme for livestock and humans, providing support for upgraded sheds, and the development of practical and feasible strategies that focus on specific animals and clusters of the national park are needed to reduce conflicts to maintain the co-existence between wildlife and human beings.