Plasmodium falciparum, humankind’s deadliest parasite, orchestrates precisely timed developmental transitions, yet the molecular mechanisms orchestrating these shifts have remained elusive. We identify the PfGID E3 ubiquitin ligase complex as a master regulator of sexual development in P. falciparum, revealing a sophisticated multi-tiered control system integrating protein degradation and RNA regulation. The PfGID complex is required for gametocyte maturation and parasite transmission to mosquitoes, underscoring its pivotal role. PfGID governs gametocyte development by fine-tuning levels of two substrates: GD1, a novel RNA-binding protein, and PfDPL, a cryptochrome-like protein. GD1 is a key regulator of P-body dynamics by maintaining the delicate balance of translational repression essential for gametocyte maturation. Our findings reveal PfDPL regulates expression of male-specific proteins essential for gametogenesis. These findings illuminate the intricate molecular choreography underlying Plasmodium sexual development and provide insights into how single-celled eukaryotes execute cell-fate programs to navigate complex life cycles and adapt to diverse host environments.