Zika virus (ZIKV) infection causes congenital neurodevelopmental abnormalities, including microcephaly, yet how ZIKV alters post-transcriptional gene regulation during human brain development remains unclear. Here, we integrate virus–host interactomics, reverse genetics, m⁶A profiling, and human brain organoid models to investigate ZIKV regulation of the host m⁶A machinery. We find that the ZIKV envelope protein (E) interacts with METTL3, promoting its cytoplasmic redistribution and disrupting METTL3-METTL14 complex formation, thereby remodeling host m⁶A methylation. Transcriptome-wide analyses further indicate that these m⁶A changes are associated with altered RNA stability among transcripts linked to neurodevelopmental processes and immune-response pathways. Structure–function analysis identifies Asn238 of ZIKV-E as a key determinant of METTL3 interaction. A recombinant ZIKV-N238A mutant exhibits comparable replication kinetics but reduced METTL3 binding and relocalization. In human brain organoids, N238A partially attenuates ZIKV-induced cortical abnormalities, while analyses in neural progenitor and microglial cells show reduced effects on m⁶A enrichment and RNA stability. Together, these findings suggest that ZIKV-mediated disruption of METTL3-dependent m⁶A regulation contributes to neurodevelopmental defects by reprogramming transcript-specific RNA fate.