Significance This study provides, to our knowledge, the first ultrastructural and dynamics analysis of the host red blood cell membrane of Plasmodium falciparum gametocytes, revealing reversible expansion of the spectrin–actin skeleton, accompanied by reversible modulation of skeletal coupling to the plasma membrane. We use the measured physical parameters to inform a computationally efficient coarse-grained model. This model shows that restructuring the skeletal meshwork can fully account for the observed deformability changes. We reveal a critical role for actin remodeling in driving this reversible biomechanical host cell subversion. This work provides fundamental insights into the molecular changes that underpin gametocyte survival in the circulation.