The Loricariinae belong to the Neotropical mailed catfish family Loricariidae. A first exhaustive and robust phylogeny of this group was reconstructed using mitochondrial and nuclear data. The resulting phylogeny indicated that the Harttiini tribe formed a paraphyletic assemblage, and within the Loricariini tribe, two sister subtribes were distinguished, Farlowellina and Loricariina. Subsequently using this phylogeny as exploratory tool, we demonstrated: (1) using co-inertia analysis that the diagnostic features provided to define the different genera were phylogenetically dependent; (2) using multiple co-inertia analysis that the underlying evolutionary forces shaping their diversification included intraphenotypic (morphology and genetics) and extraphenotypic (ecology and distribution) components; (3) using the RLQ analysis that co-dispersion events occurred between co-distributed species responsible for the current fish distribution; and (4) using the multi-scale pattern analysis that the co-evolution in traits related to the mouth characteristics was linked to reproductive functions responsible for a tertiary evolution of this organ.