Phenotypic plasticity allows organisms to alter their phenotype in direct response to changes in the environment. Despite growing recognition of plasticity’s role in ecology and evolution, few studies have probed plasticity’s molecular bases—especially using natural populations. We investigated the genetic basis of phenotypic plasticity in natural populations of spadefoot toads (Spea multiplicata). Spea tadpoles normally develop into an ‘omnivore’ morph that is favored in long-lasting, low-density ponds. However, if tadpoles consume freshwater shrimp or other tadpoles, they can alternatively develop (via plasticity) into a ‘carnivore’ morph that is favored in shallow, high-density ponds. By combining natural variation in pond ecology and morph production with population genetic approaches, we identified candidate loci associated with morph (carnivores versus omnivores) and loci associated with adaptive phenotypic plasticity (adaptive versus maladaptive morph choice). Our candidate morph loci mapped to two genes, whereas our candidate plasticity loci mapped to 14 genes. In both cases, the identified genes tended to have functions related to their putative role in spadefoot tadpole biology. Our results thereby form the basis for future studies into the molecular mechanisms that mediate plasticity in spadefoots. More generally, these results illustrate how diverse loci might be deployed to mediate adaptive plasticity.Phenotypic plasticity allows organisms to alter their phenotype in direct response to changes in the environment. Despite growing recognition of plasticity’s role in ecology and evolution, few studies have probed plasticity’s molecular bases—especially using natural populations. We investigated the genetic basis of phenotypic plasticity in natural populations of spadefoot toads (Spea multiplicata). Spea tadpoles normally develop into an ‘omnivore’ morph that is favored in long-lasting, low-density ponds. However, if tadpoles consume freshwater shrimp or other tadpoles, they can alternatively develop (via plasticity) into a ‘carnivore’ morph that is favored in shallow, high-density ponds. By combining natural variation in pond ecology and morph production with population genetic approaches, we identified candidate loci associated with morph (carnivores versus omnivores) and loci associated with adaptive phenotypic plasticity (adaptive versus maladaptive morph choice). Our candidate morph loci mapped to two genes, whereas our candidate plasticity loci mapped to 14 genes. In both cases, the identified genes tended to have functions related to their putative role in spadefoot tadpole biology. Our results thereby form the basis for future studies into the molecular mechanisms that mediate plasticity in spadefoots. More generally, these results illustrate how diverse loci might be deployed to mediate adaptive plasticity.