AMPA-type glutamate receptors (AMPAR) mediate excitatory cochlear transmission. However, the unique roles of AMPAR subunits are unresolved. Lack of subunit GluA3 () in male mice reduced cochlear output by 8-weeks of age. Since is X-linked and considering sex differences in hearing vulnerability, we hypothesized accelerated presbycusis in females. Here, auditory brainstem responses (ABR) were similar in 3-week-old female and mice. However, when raised in ambient sound, ABR thresholds were elevated and wave-1 amplitudes were diminished at 5-weeks and older in . In contrast, these metrics were similar between genotypes when raised in quiet. Paired synapses were similar in number, but lone ribbons and ribbonless synapses were increased in female mice in ambient sound compared to or to either genotype raised in quiet. Synaptic GluA4:GluA2 ratios increased relative to , particularly in ambient sound, suggesting an activity-dependent increase in calcium-permeable AMPARs in . Swollen afferent terminals were observed by 5-weeks only in females reared in ambient sound. We propose that lack of GluA3 induces sex-dependent vulnerability to AMPAR-mediated excitotoxicity.