Distributional limits of many tropical species in Florida are ultimately determined by tolerance to low temperature. An unprecedented cold spell during 2–11 January 2010, in South Florida provided an opportunity to compare the responses of tropical American crocodiles with warm-temperate American alligators and to compare the responses of nonnative Burmese pythons with native warm-temperate snakes exposed to prolonged cold temperatures. After the January 2010 cold spell, a record number of American crocodiles (n = 151) and Burmese pythons (n = 36) were found dead. In contrast, no American alligators and no native snakes were found dead. American alligators and American crocodiles behaved differently during the cold spell. American alligators stopped basking and retreated to warmer water. American crocodiles apparently continued to bask during extreme cold temperatures resulting in lethal body temperatures. The mortality of Burmese pythons compared to the absence of mortality for native snakes suggests that the current population of Burmese pythons in the Everglades is less tolerant of cold temperatures than native snakes. Burmese pythons introduced from other parts of their native range may be more tolerant of cold temperatures. We documented the direct effects of cold temperatures on crocodiles and pythons; however, evidence of long-term effects of cold temperature on their populations within their established ranges remains lacking. Mortality of crocodiles and pythons outside of their current established range may be more important in setting distributional limits.