Plasmodium falciparum, a lethal protozoan, undergoes a complex extra- and intraerythrocytic development cycle that requires intricate and flexible regulatory mechanisms in order to facilitate reproduction and maintain the parasite’s resistance to environmental stress. Protein post-translational modifications (PTMs) are essential processes following protein biogenesis that allow proteins to fulfill their diverse biological functions. Here, we present comprehensive PTMomic profiling of both P. falciparum and its erythrocytic host cells during the 48 hours after infection. Fine mappings of each protein in both P. falciparum and the infected red blood cells (pRBCs) were accomplished. More than two-thirds of the parasite and its host cell proteins underwent extensive and dynamic modification throughout the erythrocytic developmental stage of the malarial parasite. Apart from the finding that PTMs actively regulated P. falciparum gene activation and silencing, the key molecules involved in the host-parasite interaction and pathogenesis were essentially modified. The establishment of an atlas of PTMomes of P. falciparum and its host erythrocytes will promote a deeper understanding of the parasite biology and will provide a basis for the search for novel antimalarials.