<p>The uplift of the Tibetan Plateau altered the environmental conditions of the local area substantially. Here, we conducted a comprehensive investigation based on morphometrics, population genomics, and climatic factors to evaluate phenotypic and genome-level variations in a radiation of <em>Chimarrichthys</em> catfish endemic to the Plateau. Discriminant function analysis showed phenotypic differences of <em>Chimarrichthys</em> between rivers with respect to elevation. Genetic structure analysis based on 6606 single nucleotide polymorphisms (SNPs) deduced genetic differences between rivers, and species delimitation indicated that the <em>Chimarrichthys</em> fish complex could be divided into three species. Restriction site-associated DNA tags were mapped to the gene sets of <em>Glyptosternon maculatum</em>, and matches were searched against databases for Gene Ontology annotation. Genomic regions exhibiting marked differences among localities represented a range of biological functions, including growth (<em>gdf11</em>), bone development (<em>bmp8a</em>), cellular response to light stimulus (<em>opn3</em>), regulation of the rhodopsin-mediated signalling pathway (<em>grk1</em>), immune response (<em>rag1</em> and <em>ung</em>), reproductive process (<em>antxr2</em>), and regulation of intracellular iron levels (<em>ireb2</em>). The tag44126, where gene <em>gdf11</em> is located, was identified as an outlier exhibiting divergence between rivers with altitude differences, and the SNP is thymine (T) in Dadu and Yalong River (~2700 m), but guanine (G) in Jinsha and Qingyi rivers (~2200 and ~ 684 m), suggesting a possible effect of altitude on its differentiation.</p>