Next generation malaria vaccines that can inhibit multiple parasite life-cycle stages and species are highly desired to progress malaria elimination. In P. falciparum, the pentameric PTRAMP-CSS-Ripr-CyRPA-Rh5 (PCRCR) complex is essential for invasion into red blood cells. Rh5, CyRPA and Ripr are leading blood-stage vaccine candidates that have been well characterised in comparison to PTRAMP-CSS. Although nanobodies raised to PTRAMP-CSS have been shown to be growth inhibitory, these were of moderate efficacy. Furthermore, the expression and function of the PCRCR complex in both the pre-erythrocytic and mosquito-stages of the parasite, and whether we could potentially prevent transmission of malaria using PCRCR specific biologics has not been explored. Here, we characterise an extensive panel of nanobodies raised to the PTRAMP-CSS complex that are more potent than any described to date. We identified three invasion inhibitory epitopes on CSS and two on PTRAMP that are highly conserved across P. falciparum strains. The crystal structures of all inhibitory nanobodies to PTRAMP-CSS and two non-inhibitory nanobodies to PTRAMP have been solved which has significant implications for structure-guided design of immunogens to the PCRCR complex. We have additionally engineered nanobody-Fc (Nb-Fc) fusion proteins and have found that PTRAMP-CSS specific Nb-Fcs are able to prevent transmission of the parasite in the mosquito stages. This highlights the potential of the PCRCR complex as a multi-stage vaccine target.