The main objective of this study was to determine the best vegetable oils (VO) for nutrition of African catfish by assessing the effects of a complete replacement of fish oil (FO) by different VO sources on its growth performance, fatty acid composition, and elongase-desaturase gene expression levels. Fish (16.2 g of initial body weight) were fed with five experimental isonitrogenous, isolipidic, and isoenergetic diets in which FO was totally replaced by cottonseed oil (CO), palm oil (PO), desert date oil (DO), or Shea butter (SB). Complete replacement of FO with VO did not affect growth performance except for low values in fish fed SB diet. Muscle n-3 LC-polyunsaturated fatty acids (PUFA) were significantly reduced in fish fed VO-based diets when compared with FO fed fish. However, the muscle arachidinic acid (ARA) levels in phospholipid class were 1.4 to 1.6 times higher in fish fed CO and DO diets than FO fed fish despite the lower ARA suppliers from these VO-based diets, suggesting endogenous LC-PUFA biosynthesis from PUFA precursors in fish fed these VO. The fads2 and elovl5 gene expression levels in liver of fish fed DO were also higher compared to FO controls. Therefore, all the results support the hypothesis that African catfish has higher biosynthesis capacity to convert vegetable n-6 PUFA precursors like linoleic acid (LNA, 18:2n-6) into n-6 LC-PUFA of the ARA type, compared to the conversion of vegetable α-linolenic acid (ALA, 18:3n-3) into n-3 LC-PUFA of the eicosapentanoic acid (EPA) or docosahexanoic acid (DHA) type. The results also indicate that DO can be recommended as the best alternative to FO replacement in African catfish nutrition.