Neisseria gonorrhoeae (Ng) has adapted numerous mechanisms to evade immune detection and subvert innate immunity to promote its own survival while residing on mucosal surfaces. Cyclic fluctuations in sex hormone levels contribute to the immunological landscape of the female reproductive tract, but the mechanisms remain to be fully elucidated. Among type I interferons, IFNe is unique in being constitutively expressed, and hormonally regulated, by epithelia of the female reproductive tract. Contrary to its reported protective role against viral and bacterial infections, we previously discovered that IFNe promotes Ng survival in a mouse vaginal colonization model via enhanced sialylation of lipooligosaccharide, which confers protection against cathelicidin- and complement-mediated killing. Using a primary cervical epithelial (Pex) cell model cultured under physiological concentrations of estradiol (E2) plus progesterone (P4) to mimic the female menstrual cycle, here we sought to determine whether IFNe modulates human cervical infection by Ng and, if so, whether these processes are regulated by E2+P4. Although IFNe is not known to be induced in response to infection or pathogen recognition receptor ligands, ELISA analysis revealed that gonococcal infection promoted IFNe protein production by Pex cells. IFNe production was enhanced under P4-predominat conditions and promoted Ng survival during infection. Blocking the IFNe-IFNAR signaling pathway, using an anti-IFNe antibody or an inhibitor of the IFNe receptor, IFNAR, resulted in decreased Ng survival but also dampened complement receptor 3 (CR3) activation on Pex cells in response to infection. CR3 is an immunomodulatory protein known to play diverse roles in innate immunity; it is also the primary receptor mediating Ng infection of Pex cells and in women with gonococcal cervicitis. Contrary to our prior work in mice, lipooligosaccharide sialylation did not substantively contribute to Ng survival during Pex cell infection. Collectively, our data demonstrate pathogen-induced, IFNe expression for the first time. Further, although they support our prior data from a mouse infection model, they also suggest that Ng may uniquely resist antimicrobial IFNe host responses using both lipooligosaccharide sialylation-dependent and -independent mechanisms. Additionally, our data identify a role for crosstalk between IFNAR- and CR3-dependent host responses in, paradoxically, promoting gonococcal cervical infection.