Alzheimer’s disease (AD) is a pervasive neurodegenerative disorder that disproportionately affects women. Since neural anatomy and disease pathophysiology differ by sex, investigating sex-specific mechanisms in AD pathophysiology can inform new therapeutic approaches for both sexes. Here, we utilized nearly 74,000 cells from human prefrontal and entorhinal cortex samples from the first two publicly available single-cell RNA sequencing AD datasets to study cell type-specific sex-stratified transcriptomic perturbations in AD. Our examination at the single-cell level revealed that sex-specific gene and pathway differences in AD were most prominently observed in glial cells of the prefrontal cortex. In the entorhinal cortex, we observed the same genes and pathways to be perturbed in opposing directions between sexes in AD relative to healthy state. Our findings contribute to growing evidence of sex differences in AD-related transcriptomic changes, which can fuel the development of therapies that may prove more effective at reversing AD pathophysiology.