The ability of animals to adapt to climate change is dependent on the extent of genetically based variation in key phenotypic traits and the nature of genetic associations between them. For aquatic organisms, upper thermal tolerance and hypoxia tolerance are traits that may affect sensitivity to climate change. To determine the genetic basis of these traits and to detect associations between them, we compared naturally occurring populations of two subspecies of Atlantic killifish, Fundulus heteroclitus, that differ in both thermal and hypoxia tolerance. Among populations, upper thermal tolerance varied approximately linearly with latitude, whereas hypoxia tolerance exhibited a steep phenotypic break across the contact zone between the subspecies, suggesting that these traits are not associated. Similarly, these traits were not correlated at the individual level in an admixed population from the contact zone. Both upper thermal tolerance and hypoxia tolerance were polygenic with variation in 47 of the 77,084 nuclear single nucleotide polymorphisms (SNPs) examined in the study explaining 43.4% of the phenotypic variation in thermal tolerance, and variation in 35 of the SNPs explaining 51.9% of the variation in hypoxia tolerance. There was no overlap in the explanatory SNPs between the traits. These results suggest that upper thermal tolerance and hypoxia tolerance are not phenotypically or genetically associated, and thus that rates of adaptive change in these traits can be independently fine-tuned by natural selection. This modularity of important physiological traits can underpin the evolvability of organisms to complex future environmental change.