Coral reefs have been rapidly deteriorating, worldwide, due to global warming, ocean acidification, bleaching, diseases, and various local anthropogenic stressors, such as coastal development, habitat destruction, overfishing and eutrophication, all of which have significantly impacted the metabolic functions of corals and other marine organisms. Global warming has been identified as the main culprit in the decline of coral reefs. In response, we assessed the metabolic responses of one of the most iconic Caribbean corals to elevated temperatures. Accordingly, the proteomic profile of Acropora palmata was investigated during the cool dry and hot wet seasons of 2014 and 2015 in Puerto Rico using a combination of two-dimensional gel electrophoresis (2D-GE) and mass spectrometry. The study revealed that the average number of differentially abundant proteoforms between seasons was 527 in the inner-shelf reef at Enrique and 1,115 in the mid-shelf reef at San Cristobal, both located on the insular shelf of southwestern Puerto Rico. Our results show significant changes in A. palmata’s proteome, inducing alterations in key metabolic, enzymatic, translational, and apoptotic processes, between the cool dry and hot wet seasons. Quantitative real-time reverse transcription PCR (qRT-PCR) was used to validate the variation in the expression of five candidate stress-related genes under different seasonal temperatures. The findings highlight key proteoforms whose abundance varied with temperature, offering insight into A. palmata’s metabolic capacity to acclimate and respond to seasonal temperature fluctuations.