Injury and death from wildlife attacks often result in people feeling violent resentment and hostility against the wildlife involved and, therefore, may undermine public support for conservation. Although Nepal, with rich biodiversity, is doing well in its conservation efforts, human-wildlife conflicts have been a major challenge in recent years. The lack of detailed information on the spatial and temporal patterns of human-wildlife conflicts at the national level impedes the development of effective conflict mitigation plans. We examined patterns of human injury and death caused by large mammals using data from attack events and their spatiotemporal dimensions collected from a national survey of data available in Nepal over five years (2010–2014). Data were analyzed using logistic regression and chi-square or Fisher's exact tests. The results show that Asiatic elephants and common leopards are most commonly involved in attacks on people in terms of attack frequency and fatalities. Although one-horned rhinoceros and bears had a higher frequency of attacks than Bengal tigers, tigers caused more fatalities than each of these two species. Attacks by elephants peaked in winter and most frequently occurred outside protected areas in human settlements. Leopard attacks occurred almost entirely outside protected areas, and a significantly greater number of attacks occurred in human settlements. Attacks by one-horned rhinoceros and tigers were higher in the winter, mainly in forests inside protected areas; similarly, attacks by bears occurred mostly within protected areas. We found that human settlements are increasingly becoming conflict hotspots, with burgeoning incidents involving elephants and leopards. We conclude that species-specific conservation strategies are urgently needed, particularly for leopards and elephants. The implications of our findings for minimizing conflicts and conserving these imperiled species are discussed.