Serpentinized rocks closely associated with Paleoproterozoic eclogitic metabasites were recently discovered at Eseka area in the northwestern edge of the Congo craton in southern Cameroon. Here, we present new field data, petrography, and first comprehensible whole-rock geochemistry data and discuss the protolith and tectonic significance of these serpentinites in the region. The studied rock samples are characterized by pseudomorphic textures, including mesh microstructure formed by serpentine intergrowths with cores of olivine, bastites after pyroxene. Antigorite constitutes almost the whole bulk of the rocks and is associated (to the less amount) with tremolite, talc, spinel, and magnetite. Whole-rock chemistry of the Eseka serpentinites led to the distinction of two types. Type 1 has high MgO (> 40 wt%) content and high Mg# values (88.80) whereas Type 2 serpentinite samples display relatively low MgO concentration and Mg# values (< 40 and 82.88 wt%, respectively). Both types have low Al/Si and high Mg/Si ratios than the primitive mantle, reflecting a refractory abyssal mantle peridotite protolith. Partial melting modeling indicates that these rocks were derived from melting of spinel peridotite before serpentinization. Bulk rock high-Ti content is similar to the values of subducted serpentinites (> 50 ppm). This similarity, associated with the high Cr contents, spinel-peridotite protolith compositions and Mg/Si and Al/Si ratios imply that the studied serpentinites were formed in a subduction-related environment. The U-shaped chondrite normalized-REE patterns of serpentinized peridotites, coupled with similar enrichments in LREE and HFSE, suggest the refertilized nature due to melt/rock interaction prior to serpentinization. Based on the results, we suggest that the Eseka serpentinized peridotites are mantle residues that suffered a high degree of partial melting in a subduction-related environment, especially in Supra Subduction Zone setting. These new findings suggest that the Nyong series in Cameroon represents an uncontested Paleoproterozoic suture zone between the Congo craton and the São Francisco craton in Brazil.