The Cretaceous and Neogene deposits from the Mamfe Basin consisting of sandstone, shale and claystone were studied using petrography, and major, traces and REEs analyses to address sediment source, environment setting, prevailing paleoclimate as well as tectonic regime of the basin. The angular to subangular shape of detrital grains reflects the mineralogical and textural immaturity of sediments and the proximity of the sediment supply source. Sedimentary rocks are composed of a significant number of lithic debris, organic matter, ostracods as well as subrounded heavy minerals referring to notable igneous and metamorphic rocks bordering the Mamfe Basin. The plots of major element ratios including iron oxide/potasium oxide (Fe2O/K2O) against silicium oxide/aluminium oxide (SiO2/Al2O3) combined with that of sodium oxide/potassium oxide (Na2O/K2O) compared to silicium oxide/aluminium oxide (SiO2/Al2O3) are characteristic of greywacke and shale with few arkoses. The pronounced Eu negative anomaly of chondrite normalized REEs along with the plot of La/Th vs Hf and Co/Th vs La/Sc suggest that sediments are in general from felsic and intermediate source rock provenance, only subordinated contribution of mafic source. The negative anomaly of Yb suggests igneous fractionation under highly reducing conditions. The chemical index of alteration values of 47–70 combined with chemical index of weathering values of 0.6–84 suggest low to moderate weathering process of the sediment in the basin. This result is further confirmed by an index of chemical variability values of 0.6–100 and Zr/Sc ratio of 0.06–2.96. The REEs distribution displays a substantial content in LREE, low content in HREE and noticible proportion of (La/Yb)N ratio (mean >9), poor (Gd/Yb)N ratio in the Cross River Formation (mean <2) and slightly moderate (Gd/Yb)N ratio in the other formations (mean >2). This result implies that sediments from the Ngeme, Nfaitok and Baso formations derived from post-Archean rocks. Geochemical paleoenvironmental proxies including Sr/Cu, Sr/Ba, Ga/Rb vs Sr/Cu and SiO2 vs K2O + NaO2+Al2O3 are in favor of arid to semi-arid conditions during the deposition. Trace Elemental ratios such as Sr/Cu, Sr/Ba, V/Ni, U/Th, Ni/Co, V/Sc, and V/Cr values indicate a predominance of oxic conditions during deposition. In contrast, some authigenic pyrite, hematite, siderite and vivianite which are iron-rich minerals suggests episodic reducing conditions in the basin. The study provides a valuable information in evaluating sediments source, depositional environment, tectonic regime as well as the paleoclimatic conditions prevailing in the basin during the depositional period. The geochemistry of rocks of the Ngeme and Baso formations suggest passive continental margin setting and Ngeme, Nfaitok and Cross River formations suggest oceanic island Arc tectonic setting.