Malaria, that ancient infectious disease is considered a great health problem due to its highly infectious and mortality rates. The more harmful kind of malaria is Plasmodium falciparum (Pf), accounting for over 1M fatalities yearly; unfortunately, existing medication regimens are hampered by resistance, necessitating the identification of novel targets against plasmodium species. Since the malaria parasite cannot recover pyrimidines, it must rely on de novo production to survive. Dihydroorotate dehydrogenase (DHODH), which facilitates the rate-limiting phase of that process, is therefore an interesting antimalarial target. In this context, computational screening comprising pharmacophore mapping, molecular docking, MM-GBSA calculations, ADME filtering and molecular dynamics were performed in order to identify novel and powerful PfDHODH inhibitors. A pharmacophore hypothesis with seven features was created and tested on 2 million compounds from the enamine database. Docking, MM-GBSA calculations, and ADME revealed ten hits with strong binding affinities and potential, stable binding energy, and drug-like properties. The top three hits were confirmed further using molecular dynamics simulations, which revealed that three of them were stable for the whole 100 ns simulation time. Relying on these findings, we recommend that Z1481646084, Z24317941, and Z951873618 be submitted for experimental verification as promising antimalarial gents.