The Upper Cretaceous successions of Wadi Umm-Khayshar, southern Galala Plateau, North Eastern Desert, Egypt, are composed of highly diversified faunas and subdivided from base to top into the Galala (Middle–Late Cenomanian), Maghra El Hadida (Latest Cenomanian–Late Turonian), Matulla (Coniacian–Santonian), and Sudr (Campanian–Maastrichtian) formations. Five ammonite biozones are recorded in the studied section: Neolobites vibrayeanus, Vascoceras cauvini (late Cenomanian), Vascoceras proprium, Choffaticeras segne, and Coilopoceras requienianum (Turonian) zones. The paleoenvironments of the Upper Cretaceous succession are interpreted based on detailed study and microfacies analysis that reflect a deposition in a homoclinal ramp platform ranging from intertidal to deep subtidal. The paleoecology of the Cenomanian–Turonian succession in the studied section is explained based on a detailed study of macrofaunal associations and sedimentary facies. Quantitative analysis (Q-mode cluster analysis, using the Raup–Crick Paired group method) of 1029 macrobenthic specimens, including 45 species of mollusks and echinoids yielded five macrofaunal associations (A–E) that are described and interpreted as remnants of communities. The nektonic elements are represented by 235 cephalopod specimens of 20 species; heatmap cluster analyses show the distribution of these specimens during the Upper Cenomanian–Turonian stages. Environmental parameters (substrate consistency, rate of sedimentation, water energy, surface-water productivity, and oxygen availability) controlled the distribution of the studied macrofauna. The five associations are divided into two major groups: low-stress associations (A, B, C, and D), and a high-stress association (E). The low stress associations are recorded from two different habitats: (1) a high-energy, firm substrate habitat, dominated by epifaunal bivalves, large epifaunal gastropods and a regular echinoid; (2) a low-energy, soft substrate habitat dominated by infaunal bivalves and echinoids. The high stress association is dominated by only two species and recorded from a high-energy shoal environment during a regression phase. A detailed study of macrobenthos and cephalopods provides a good paleoecological understanding of Cenomanian–Turonian succession in the Wadi Umm–Khayshar section.