Coral reefs of the Florida Keys typically experience seasonal temperatures of 20–31 °C. Deviation outside this range causes physiological impairment of reef-building corals, potentially leading to coral colony death. In January and February 2010, two closely spaced cold fronts, possibly driven by an unusually extreme Arctic Oscillation, caused sudden and severe seawater temperature declines in the Florida Keys. Inshore coral reefs [e.g., Admiral Reef (ADM)] experienced lower sustained temperatures (i.e., < 12 °C) than those further offshore [e.g., Little Grecian Reef (LG), minimum temperature = 17.2 °C]. During February and March 2010, we surveyed ADM and observed a mass die-off of reef-building corals, whereas 12 km away LG did not exhibit coral mortality. We subsequently measured the physiological effects of low-temperature stress on three common reef-building corals (i.e., Montastraea faveolata, Porites astreoides, and Siderastrea siderea) over a range of temperatures that replicated the inshore cold-water anomaly (i.e., from 20 to 16 to 12 °C and back to 20 °C). Throughout the temperature modulations, coral respiration as well as endosymbiont gross photosynthesis and maximum quantum efficiency of photosystem II were measured. In addition, Symbiodinium genotypic identity, cell densities, and chlorophyll a content were determined at the beginning and conclusion of the experiment. All corals were significantly affected at 12 °C, but species-specific physiological responses were found indicating different coral and/or Symbiodinium cold tolerances. Montastraea faveolata and P. astreoides appeared to be most negatively impacted because, upon return to 20 °C, significant reductions in gross photosynthesis and dark respiration persisted. Siderastrea siderea, however, readily recovered to pre-treatment rates of dark respiration and gross photosynthesis. Visual surveys of inshore reefs corroborated these results, with S. siderea being minimally affected by the cold-water anomaly, whereas M. faveolata and P. astreoides exhibited nearly 100% mortality. This study highlights the importance of understanding the physiological attributes of genotypically distinct coral-Symbiodinium symbioses that contribute to tolerance, recovery, and consequences to an environmental perturbation. These data also document effects of a rarely studied environmental stressor, possibly initiated by remote global climate events, on coral-Symbiodinium symbioses and coral reef communities.