Domestication in fish involves rapid and complex changes in life-history, physiology and behavior under human-controlled aquaculture conditions. In gilthead seabream (Sparus aurata), a species with a relatively recent domestication history, we used genome-wide population comparisons to show that domestication targets a core set of highly conserved regulators of environmental sensing mechanisms. Across farmed stocks and wild populations spanning the Mediterranean, our analyses reveal divergence at key genes involved in pathways that translate oxygen and chemical cues into stress, immune, endocrine and reproductive outcomes. Standout candidates include ahrra within the ancient AHR–ARNT/HIF signaling system, kdm6al, a chromatin regulator coordinating developmental and stress responses, and pigm, a GPI-anchor biosynthesis gene shaping cell-surface composition and host defense. These functions are shared widely across animals, from invertebrates to vertebrates, suggesting that domestication often proceeds by tuning long-standing sensory circuitry to aquaculture conditions. This convergence points to a measure of predictability in the genomic response to captivity, links molecular pathways to production-relevant traits such as stress tolerance and reproduction, and offers actionable hypotheses for rapid adaptation in species during domestication. By identifying these conserved regulators through empirical data, our results connect microevolution under domestication with fundamental biology and provide tractable gene sets for testing how ancient pathways are repurposed during contemporary evolution and for monitoring in aquaculture.Domestication in fish involves rapid and complex changes in life-history, physiology and behavior under human-controlled aquaculture conditions. In gilthead seabream (Sparus aurata), a species with a relatively recent domestication history, we used genome-wide population comparisons to show that domestication targets a core set of highly conserved regulators of environmental sensing mechanisms. Across farmed stocks and wild populations spanning the Mediterranean, our analyses reveal divergence at key genes involved in pathways that translate oxygen and chemical cues into stress, immune, endocrine and reproductive outcomes. Standout candidates include ahrra within the ancient AHR–ARNT/HIF signaling system, kdm6al, a chromatin regulator coordinating developmental and stress responses, and pigm, a GPI-anchor biosynthesis gene shaping cell-surface composition and host defense. These functions are shared widely across animals, from invertebrates to vertebrates, suggesting that domestication often proceeds by tuning long-standing sensory circuitry to aquaculture conditions. This convergence points to a measure of predictability in the genomic response to captivity, links molecular pathways to production-relevant traits such as stress tolerance and reproduction, and offers actionable hypotheses for rapid adaptation in species during domestication. By identifying these conserved regulators through empirical data, our results connect microevolution under domestication with fundamental biology and provide tractable gene sets for testing how ancient pathways are repurposed during contemporary evolution and for monitoring in aquaculture.