The increasing concentration of CO2 in the atmosphere and resulting flux into the oceans will further exacerbate acidification already threatening coastal marine ecosystems. The subsequent alterations in carbonate chemistry can have deleterious impacts on many economically and ecologically important species including the northern quahog (Mercenaria mercenaria). The accelerated pace of these changes requires an understanding of how or if species and populations will be able to acclimate or adapt to such swift environmental alterations. Thus far, studies have primarily focused on the physiological effects of ocean acidification (OA) on M. mercenaria, including reductions in growth and survival. However, the molecular mechanisms of resilience to OA in this species remains unclear. Clam gametes were fertilized under normal pCO2 and reared under acidified (pH ~ 7.5, pCO2 ~ 1200 ppm) or control (pH ~ 7.9, pCO2 ~ 600 ppm) conditions before sampled at 2 days (larvae), 32 days (postsets), 5 and 10 months (juveniles) and submitted to RNA and DNA sequencing to evaluate alterations in gene expression and genetic variations. Results showed significant shift in gene expression profiles among clams reared in acidified conditions as compared to their respective controls. At 10 months of exposure, significant shifts in allele frequency of single nucleotide polymorphisms (SNPs) were identified. Both approaches highlighted genes coding for proteins related to shell formation, bicarbonate transport, cytoskeleton, immunity/stress, and metabolism, illustrating the role these pathways play in resilience to OA.