Morocco is a very rich country in terms of wetlands, including bays, estuaries, lagoons, lakes, and rivers, among others. However, many of them need to be well managed and better exploited, thus requiring baseline descriptive studies to assess faunal patterns and trends. Oualidia lagoon is not an exception. In fact, the studies conducted to date in the lagoon mainly focused on its oceanographic features and aquaculture capacities. The present paper presents the first study on the whole macrofaunal assemblages of Oualidia lagoon, having as main objectives analyze the composition and structure of the assemblages, as well as their relationships with the main environmental variables explaining their spatial distribution variability in the enclosed ecosystem of the Oualidia coastal lagoon. The benthic macroinvertebrates of Oualidia lagoon were studied in summer 2013 based on 43 stations spread over the whole lagoon by using a Van Veen grab. Two replicate samples were collected for macrobenthos and one additional replicate for sediment analyses at each station. Also, single water salinity and temperature measurements were recorded at each station. Fifty-one species from seven different taxa were recorded, among which mollusks (37%), polychaetes (25%) and crustaceans (25%) dominated in terms of species number. Peringia ulvae, Abra alba, Sphaeroma serratum, Cerastoderma edule and Corophium sp. accounted for 88% of total abundance. The benthos was structured along a downstream–upstream gradient, showing three assemblages, named according to the IndVal index: (1) Diopatra cf. marocensis, (2) Peringia ulvae, and (3) Cerastoderma edule, while the main factors driving their distribution were granulometry and salinity. The Biotic and Environmental analysis showed that the combination of granulometry and salinity was the major factors controlling the spatial distribution of the macrozoobenthos in the Oualidia Lagoon.