Abstract Synodontis Cuvier, 1816 is a species-rich group of African catfishes. Prior to this analysis, 13 species of Synodontis were recognized from Lake Tanganyika and its tributaries, composing the only extant lacustrine radiation of the genus, with a unique origin of obligate brood parasitism among all fishes. Species differentiation and phylogenetic relationships of this group remained largely unresolved. Herein, the taxonomy of Synodontis in the Lake Tanganyika basin is revised, including redescriptions of all species and an updated identification key. Genetic (mitochondrial and nuclear genomic markers) and morphological data suggest a lower species diversity than previously recognized, supporting the distinction of 10 Synodontis species in the lake basin. Based on our findings, we recognize Synodontis grandiops, Synodontis ilebrevis, and Synodontis lucipinnis as junior synonyms of Synodontis multipunctatus, Synodontis polli, and Synodontis petricola, respectively. No recent material of Synodontis dhonti and Synodontis tanganyicae (with Synodontis lacustricolus as a synonym) was available. Morphometric/meristic data suggest their close relationship to Synodontis granulosus. Sequencing of historical specimens inferred S. tanganyicae as sister to S. granulosus but with a 1.7% divergence based on mitochondrial data. In contrast to previous studies, phylogenomic data support the lacustrine assemblage of Synodontis in Lake Tanganyika as monophyletic.