Negative interactions between people and crocodilians have increased worldwide, but in Mexico there have been few systematic reports and no rigorous evaluation of this problem. We compiled information on negative interactions between people and the spectacled caiman Caiman crocodilus and American crocodile Crocodylus acutus from the Worldwide Crocodilian Attack Database for 1993–2018, and we investigated interactions in greater depth, through interviews with people in La Encrucijada Biosphere Reserve. We examined the relationship between the occurrence of negative interactions between people and C. acutus and the species' nesting season and abundance, and presence records. In Mexico, the frequency of negative interactions increases when anthropogenic activities occur close to nesting sites (< 30 km) and during the nesting season (February–September). In La Encrucijada, following negative interactions with crocodiles, the local inhabitants killed 30 crocodiles measuring > 2.5 m long in 2011–2012. The frequency of negative human–crocodilian interactions was not correlated with the abundance of crocodilians but was correlated with the number of presence records of crocodiles. Strategies to minimize these interactions include warnings at nesting sites, increased monitoring of anthropogenic activities during the nesting season, and management of nests to prevent them being destroyed by people.