This study focuses on risk assessment of Cr, V, Ni, Co, Pb, Cu, and Zn in the Mefou River sediments located at Yaoundé, West-Africa. Sediment samples were collected from five stations in the downstream of the Mefou River, which drains the urban area of Yaoundé between latitudes 3°30′ and 3°58′ North and longitudes 11°20′ and 11°40′ East. The geochemistry data were analyzed statistically and the pollution indices were calculated in order to identify and estimate the sources of metal contamination in the Mefou River sediments. The results obtained show that the average concentrations of trace metals are almost higher than those of the upper continental crust (UCC) and the metal average in the Simbock Lake cores. However, the concentrations of Ni, Cu, Pb, and Zn in sediments located in most urbanized sites are lower than those of the UCC and the average of Simbock Lake sediments. The pollution indices such as enrichment factor (EF), geo-accumulation index (Igeo), and pollution load index (PLI) showed that trace metals were mainly influenced by human sources, except for Pb, Cu, and Zn, which stemmed from natural sources. The sediments of the Mefou River would therefore be affected with low to moderate pollution levels. The low values of potential ecological risk (RI: 22.36–41.53) suggest a low potential ecological risk effect. The multivariate statistical analysis indicates that Ni, Cu, Pb, Co, and Zn have been derived mainly from natural sources, while V and Cr would partially derive from human activities. The results of this research can be a reference for trace metal pollution along an African urbanized river corridor. This can be considered as an act of prevention of urban watercourses in Cameroon and in other parts of the world, especially in major African urban metropolis.