In a ten second period immediately prior to erythrocyte invasion, Plasmodium falciparum merozoites undergo four seemingly distinct receptor-ligand events. By specific ablation and filming of the resultant phenotype, we show that these interactions occur in the following order: (1) an MSP1-mediated interaction, (2) the EBA/Rh-mediated ‘alternate pathways’, (3) PfRh5 to basigin binding and (4) the AMA1 to RON2 interaction. We demonstrate that during this pre-invasion period vigorous erythrocyte deformation strongly favours successful invasion. This deformation requires the EBA/PfRh ligands acting in concert with the actomyosin motor. Downstream, PfRh5 binding to the erythrocyte basigin receptor triggers the release of calcium from parasite to host cell, which in turn leads to the dehydration of infected erythrocytes observed immediately after invasion. This data suggests that PfRh5-basigin binding forms a cytoplasmic continuity between parasite and host membranes and shows that this occurs prior to AMA1-RON2 mediated tight junction formation. This work provides a rational basis to combine sequentially acting key merozoite vaccine candidates for synergistic control of P. falciparum malaria.