Plasmodium falciparum Pfs230 and Pfs48/45 are the leading candidates for malaria transmission-blocking vaccines. However, it remains unknown how the two interact and if additional domains in Pfs230 are potential vaccine candidates. Here we report a 3.36 Å resolution cryo-electron microscopy structure of the endogenous Pfs230-Pfs48/45 complex. We show that Pfs48/45 interacts with Pfs230 domains 13 and 14, which are distinct from domains included in current Pfs230 vaccine immunogens. Using a transgenic line with a domain 13 to 14 deletion, we show that these domains are essential for Pfs230 localization on the gamete surface. Nanobodies against these domains inhibit Pfs230-Pfs48/45 complex formation, reduce transmission and structural analyses reveal their binding epitopes. Pfs230 domains 13 and 14 are targets of naturally acquired immunity and when delivered as mRNA-LNP vaccines induced potent immune responses. Our comprehensive structural insights on a core P. falciparum fertilization complex guide the design of novel transmission-blocking vaccine candidates against malaria.