Here we develop a novel genetic population suppression system we term Ifegenia (Inherited Female Elimination by Genetically Encoded Nucleases to Interrupt Alleles). We demonstrate that Ifegenia can induce heritable CRISPR-knockout mutations of femaleless (fle), a gene required for female development, which in turn results in gynecide. fle-disrupted Ifegenia-derived males remain fit and reproductively viable, and can pass along fle mutations as well as the CRISPR machinery to induce subsequent fle mutations resulting in additional gynecide in future generations. Through mathematical modeling, we further demonstrate that iterative releases of Ifegenia males acts as an effective, confinable, controllable, and safe population suppression system.