The impact of ocean acidification on marine ecosystems will depend on the capacity for species to adapt. Recent studies show that the behaviour of reef fishes is impaired at projected future CO2 levels; however there is also individual variation that might promote adaptation. We used a genome-wide approach to evaluate the potential heritability of this variation in CO2 sensitivity in the spiny damselfish, Acanthochromis polyacanthus. Offspring of CO2 tolerant and CO2 sensitive parents were reared at near-future CO2 (754 μatm) or present-day control levels (414 μatm). By integrating 36 brain transcriptomes and proteomes with a de novo assembled genome we investigated the molecular responses of the fish brain to increased CO2 and the expression of parental tolerance to high CO2 in the offspring molecular phenotype. Exposure to high CO2 resulted in differential regulation of 173 and 62 genes and 109 and 68 proteins in the tolerant and sensitive groups respectively. Importantly, the majority of differences between offspring of tolerant and sensitive parents occurred in high CO2 conditions. Consequently, there was a clear signature of parental sensitivity to high CO2 in the molecular phenotype of the offspring, primarily driven by circadian rhythm genes. This transgenerational molecular signature suggests that individual variation in CO2 sensitivity could facilitate adaptation of fish populations to ocean acidification.