Polycystic ovary syndrome (PCOS) is the most common form of anovulatory infertility worldwide, affecting 1 in 10 women. Although commonly considered an ovarian disorder, the brain is a critical contributor to PCOS pathogenesis. Women with PCOS exhibit elevated cerebrospinal fluid GABA levels and preclinical models of PCOS exhibit increased GABAergic input to gonadotropin-releasing hormone neurons (GnRH-N), which orchestrate the hypothalamo-pituitary-gonadal axis. The arcuate nucleus (ARN) is postulated as the anatomical origin of elevated GABAergic innervation; however, the functional role of this circuit is undefined. The present study aimed to test the hypothesis that increased activity in ARN GABA neurons underpins the reproductive dysfunction of PCOS. To investigate the effect of selective activation of ARN GABA-N on GnRH-N activity and fertility we used chemogenetic tools coupled with a Cre-lox approach in mice. The designer receptor hM3Dq was specifically expressed in ARN GABA-N via stereotaxic injection in vesicular GABA transporter (VGAT-Cre) mice. The delivery of the designer drug (CNO) to activate hM3Dq was coupled with serial tail-tip blood sampling to measure luteinizing hormone (LH) secretion as a readout of GnRH secretion. Acute stimulation of ARN GABA fibers adjacent to GnRH neurons resulted in a significant and long-lasting increase in LH secretion. Chronic activation of ARN GABA neurons impaired estrous cyclicity, decreased corpora lutea number, increased circulating testosterone and resulted in a trend toward increased LH pulse frequency similar to the PCOS condition. Altogether, these results support the hypothesis that ARN GABA neurons are a functional component of the GnRH neuronal network and suggest that elevated activity in this circuit can drive reproductive dysfunction similar to PCOS.