Summary The RNA modification N6 -methyladenosine (m 6 A) can modulate mRNA fate and thus affect many biological processes. We analyzed m 6 A modification across the transcriptome following infection by dengue virus (DENV), Zika virus (ZIKV), West Nile virus (WNV), and hepatitis C virus (HCV). We found that infection by these viruses in the Flaviviridae family alters m 6 A modification of specific cellular transcripts, including RIOK3 and CIRBP . During viral infection, the addition of m 6 A to RIOK3 promotes its translation, while loss of m 6 A in CIRBP promotes alternative splicing. Importantly, we found that activation of innate immune sensing or the endoplasmic reticulum (ER) stress response by viral infection contributes to the changes in m 6 A modification in RIOK3 and CIRBP , respectively. Further, several transcripts with infection-altered m 6 A profiles, including RIOK3 and CIRBP , encode proteins that influence DENV, ZIKV, and HCV infection. Overall, this work reveals that cellular signaling pathways activated during viral infection lead to alterations in m 6 A modification of host mRNAs to regulate infection.