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ABSTRACT The Earth's ionosphere plays a critical role in radio wave transmission, reflection, and scattering, directly affecting communication, navigation, and positioning systems. However, the comprehensive impacts of space weather remain to be fully established in cases where the ionosphere experiences strong disturbances during geomagnetic storms. We reported unprecedented observational evidence of extreme ionospheric electron density depletion and its hemispheric asymmetry during the May 10–12, 2024 super geomagnetic storm, utilizing multi-instrument ground-based and spaceborne in-situ observations. The ionospheric electron density significantly decreased, with a maximum reduction of 98% over the whole northern hemisphere for more than 2 days, causing backscatter echo failures in multiple ionosondes within the Chinese Meridian Project (CMP) monitoring network. In contrast, mid-to-low latitude regions in the southern hemisphere exhibited electron density enhancements. Thermosphere-Ionosphere-Electrodynamics General Circulation Model (TIEGCM) simulations demonstrated strong consistency with northern hemispheric observations. The vertical drift and the column integrated ratio of O and N2 (ΣO/N2) from observations and simulations indicated the deep reduction of total electron content (TEC) mainly generated by severe ion recombination associated with neutral composition changes that interacted with the disturbed electric field. The summer to winter neutral wind and asymmetry of O/N₂ were possibly responsible for the asymmetry in electron density between the northern and southern hemispheres. These results advance understanding of ionospheric storm physics by establishing causal links between magnetosphere-thermosphere coupling processes and extreme electron density variations, while providing critical observational constraints for space weather model refinement.