The impact of the Amazon River freshwater plume on planktonic cnidarians over neritic and oceanic provinces is unknown. To provide further knowledge we took advantage of an oceanographic cruise performed in October 2012 in the Western Atlantic off the North Brazilian coast (8°N, 51°W—3.5°S, 37°W). A complex and dynamic system was observed, with strong currents and eddies dispersing the plume over a large area. Our results show that the Amazon River shapes marine habitats with a thin highly productive surface layer compressed by a deeper oxygen minimum zone both over the shelf and in the open ocean. We hypothesized that such habitat structure is particularly advantageous to planktonic cnidarians, which have low metabolic rates, being able to survive in hypoxic zones, resulting in high species richness and abundance. Over the shelf, distinctions were sharp and the area under the influence of the plume presented a diverse assemblage occurring in large abundance, while outside the plume, the hydromedusa Liriope tetraphylla was dominant and occurred almost alone. Divergences in the oceanic province were less pronounced, but still expressive being mostly related to the abundance of dominant species. We concluded that Amazon River plume is a paramount physical feature that profoundly affects the dynamics of the mesoscale habitat structure in the Western Equatorial Atlantic Ocean and that such habitat structure is responsible for shaping planktonic cnidarian assemblages both in neritic and oceanic provinces.