Qualitative phytochemical and anti-trypanosomal properties of the petroleum ether, chloroform, methanol and aqueous extracts, obtained by cold extraction from the leaves, stem bark and roots of Prosopis africana were evaluated. The methanolic and aqueous extracts of the stem bark and leaves of the plant contained alkaloids, saponins, tannins and flavonoids. Anthraquinone was present in the stem bark methanolic extract and in the methanolic and aqueous extracts of the root as well as the aqueous extract of the leaves. Resins was present in the petroleum ether and chloroform extracts of the stem bark and leaves, while tannins was detected in the methanol and aqueous extracts of the stem bark and leaves of the plant in addition to the petroleum ether and chloroform extracts of the root bark. All the solvent extracts showed strong in vitro anti-trypanosomal activity and 2 and 4 mg/ml, but in vivo only the methanolic extract of the leaves displayed the most promising anti-trypanosomal effect at 200 mg/kg dose. Hence, Prosopis africana extracts possess significant anti-trypanosomal activity to warrant bioassay-guided evaluation and identification of the active principle.