We report a systematic, cellular phenotype-based antimalarial screening of the MMV Pathogen Box collection, which facilitated the identification of specific blockers of late stage intraerythrocytic development of Plasmodium falciparum First, from standard growth inhibition assays, we identified 173 molecules with antimalarial activity (EC50 ≤ 10μM) which also includes 62 additional molecules over previously known antimalarial candidates from Pathogen Box. We identified 90 molecules with EC50 ≤ 1μM, none of them had significant effect on ring-trophozoite transition while 9 molecules inhibited trophozoite-schizont transition and 21 molecules inhibited schizont-ring transition (with ≤50% parasites failing to proceed to the next stage) at 1μM. We therefore re-screened all 173 molecules and validated in secondary assays by flow cytometry and microscopic analysis to prioritize 12 hits as selective blockers of schizont-ring transition. Seven of these molecules inhibited calcium ionophore induced egress of Toxoplasma gondii, a related apicomplexan parasite, suggesting that the inhibitors may be acting via conserved mechanism, which can be further exploited for target identification studies. We demonstrate that two molecules, MMV020670 and MMV026356, identified as schizont inhibitors in our screens, induce fragmentation of DNA in merozoites thereby impairing their ability to egress and invade. Further mechanistic studies would facilitate therapeutic exploitation of these molecules as broadly active inhibitors targeting late-stage development and egress of apicomplexan parasites relevant to human health.