The Mbal area is situated within the Neoproterozoic Lom Basin in Cameroon. The objective of this paper was to determine the level of contamination and risk associated of potentially toxic metals (PTMs) in stream sediments of Mbal. Sampling was performed by panning and collected sediment were analysed using an inductively coupled plasma-mass spectrometer. The sediment samples showed significant enrichment in mercury, above 10000 ppb. The other transition metals including manganese, zinc, lead were also elevated, ranging from 825 to 1950, 50.80 to 97 and 9.80 to 87.20 ppm, respectively. Multivariate statistical analyses revealed that the enrichment of the PTMs were attributed both to geogenic and anthropogenic sources. Pollution indicators such as degree of contamination, modified degree of contamination and pollution load index yielding 10809.33–200005, 982.67–18182.33 and 0.59–1.18 respectively, suggest high degree of sediments contamination from natural and anthropogenic sources. Geo-accumulation index and enrichment factor revealed moderate to extreme levels of metallic pollution. Potential ecological risk indices show extreme ecological risk index of PTMs suggesting ecological effects to biota and humans in the ecosystem. Mercury, lithology, mining, domestic and agricultural activities were major sources of PTMs pollution. Toxic metals may cause chronic health problems such as cardiovascular diseases, nervous system disorder, kidney damage and gastrointestinal disorder. This study underlines the importance of continuous monitoring and adaptive management for the preservation of the biotic and non-biotic environment. The results may assist mining companies and local populations in setting realistic targets for monitoring and remediation programs.