Thyroid hormone (TH) signaling plays an important role in the regulation of long-wavelength vision in vertebrates. In the retina,thyroid hormone receptor β(thrb) is required for expression of long-wavelength-sensitive opsin (lws) in red cone photoreceptors, while in retinal pigment epithelium (RPE), TH regulates expression of a cytochrome P450 enzyme,cyp27c1, that converts vitamin A1into vitamin A2to produce a red-shifted chromophore. To better understand how TH controls these processes, we analyzed the phenotype of zebrafish with mutations in the three known TH nuclear receptor transcription factors (thraa,thrab,and thrb). We found that no single TH nuclear receptor is required for TH-mediated induction ofcyp27c1but that deletion of all three (thraa−/−;thrab−/−;thrb−/−) completely abrogates its induction and the resulting conversion of A1- to A2-based retinoids. In the retina, loss ofthrbresulted in an absence of red cones at both larval and adult stages without disruption of the underlying cone mosaic. RNA-sequencing analysis revealed significant down-regulation of only five genes in adultthrb−/−retina, of which three (lws1,lws2, andmiR-726) occur in a single syntenic cluster. In thethrb−/−retina, retinal progenitors destined to become red cones were transfated into ultraviolet (UV) cones and horizontal cells. Taken together, our findings demonstrate cooperative regulation ofcyp27c1by TH receptors and a requirement forthrbin red cone fate determination. Thus, TH signaling coordinately regulates both spectral sensitivity and sensory plasticity.