Background: Combretum nigricans (Combretaceae) is a small, smooth bark tree used in traditional medicine for the treatment of prurigo, dysentery, fever and other symptoms of acute malaria in North-Central Nigeria. Materials and Methods: The antimalarial activity of C nigricans hydro-methanol crude leaf extract was evaluated against Plasmodium berghei in mice. The Peters’ 4-day suppressive test against early malaria infection and Rane’s curative test against established malaria were employed in assessing the antimalarial activity of the crude extract. In each test model, five groups containing five mice each were used. Group 1 mice were administered with 10 ml distilled water/kg b.w. p.o., groups 2 - 4 were administered with 200, 400, and 800 mg extract/kg b.w. p.o. respectively, while group 5 mice were administered with artesunate 10 mg/kg b.w. p.o. Result: All doses of C. nigricans extract employed for the study (200 – 800 mg/kg b.w. p.o.) gave significant (P<0.05) chemosuppressive effect against P. berghei, this effect was observed to be dose-related; while the 400 mg/kg extract dose gave the highest curative effect. Compared to control, the extract also prolonged the mean survival time at all doses, and as well prevented the characteristic decrease in body temperature elicited by P. berghei in mice. The LD50 of the extract was >5000 mg/kg b.w. p.o. in mice. Conclusion: The result from the study indicates that C. nigicans crude leaf extract is safe orally and possesses significant antimalarial activity.