In the present study, the antimalarial activity of the extracts and fractions of the leaves of Persea americana and Dacryodes edulis as well as their phytochemical compositions were examined. Each of the extracts of the plants was successively fractionated to obtain hexane, ethyl acetate, methanol, and water fractions. The extracts and fractions were tested against Plasmodium berghei in both curative and suppressive antimalarial mouse models. Their major phytochemical composition was studied by the standard chemical tests and HPLC analysis. The extracts and fractions of P. americana and D. edulis demonstrated significant ( p < 0.05 ) maximal plasmodial inhibition as 52.16 ± 2.77% and 57.10 ± 1.98%, respectively, and chemosuppression of parasitemia as 64.01 ± 0.08% and 71.99 ± 0.06%, respectively. The major secondary metabolites identified in the plants include alkaloids, flavonoids, and saponins. It was concluded that P. americana and D. edulis possess promising antimalarial activity and they are potential sources of new lead compounds against malaria.