We analyzed the local variation of fish assemblages in four coastal lagoon systems surrounded by mangroves, draining into the Gulf of Tehuantepec (Pacific versant of Mexico), and determined the spatial patterns of alpha, beta, and gamma diversity. Fish were sampled between 2004 and 2016 at 63 sites using cast nets. The collected data were supplemented with information obtained from published works for three other coastal lagoons for the regional analysis. Local richness was high (89 species in a total of 19,017 specimens in four systems). Locally, dissolved oxygen, depth, and distance to mangrove were variables that significantly affected richness and abundance of fish in one or more systems. The Chantuto-Panzacola system showed the highest richness, significantly different from the other systems, although the trophic groups were similar. Regionally, two, Istmo and Soconusco complexes were identified, whose turnover rate (0.36) and gamma diversity (176) increased from north to south. Fish species richness and abundance increased with growing mangrove area, both locally and regionally, making this a highly explanatory variable. The Gulf of Tehuantepec is an environmentally heterogeneous region, with ecological patterns defined according to the spatiotemporal scale, which should be considered in the delineation of ecoregions and coastal management planning.