Limbal stem cells (LSC), a population of unipotent self-renewing stem cells, maintain corneal epithelial homeostasis and warrant post-injury regeneration. Ambient ultraviolet-A (UVA) radiation is a major, omnipresent environmental hazard jeopardizing LSC function and viability. Excessive UVA exposure has been associated with increased risk of developing photodegenerative, ocular surface disorders characterized by oxidative damage, epithelial defects, and visual impairment. Nonetheless, cellular mechanism(s) constituting LSCs stress response to counteract UVA-induced reactive oxygen species and cytotoxic stress, so far, remain elusive. In this study, autophagy, a ubiquitous detoxification process governing proteostasis and various stem cell properties, was identified as a central linchpin of LSCs defense against UVA-elicited cellular stress. Antioxidant, regulatory, as well as cytoprotective functions of autophagy were revealed. Photo-activated autophagy was found essential for balancing post UVA redox status and adapting LSCs cell cycle dynamics by regulating subcellular localization of the ocular master transcription factor PAX6. By promoting PAX6 nuclear-to-cytoplasmic translocation, autophagy was crucial to enable p21-mediated cell cycle arrest in LSCs confronted with UVA stress. By comparison, autophagy deficiency resulted in perturbed redox balance and cell cycle progression of UVA-irradiated LSCs, corroborating autophagys function as a regulatory pacemaker of LSC cell cycle dynamics under UVA stress. Moreover, unfolded protein response (UPR) was implicated in LSCs cellular defense against UVA-elicited proteotoxic stress. UPR is proposed as an endoplasmic reticulum (ER) stress sensor and activates cyto-protective autophagy to alleviate proteotoxic stress. Impaired autophagy exacerbated UVA-induced ER stress and culminated in amplified UPR induction, suggesting that an intricate crosstalk between autophagy and UPR fine-tunes the global ER stress response of UVA-stressed LSCs. Taken together, results presented in this work identified molecular mechanisms implicated in LSCs defense against UVA-induced cyto- and proteotoxic stress and contribute to a better understanding of UVA-related corneal pathology and disease etiology. Modulators targeting the integrated UVA stress response of LSCs harbor promising potential to prevent and/or treat UVA-associated LSC ocular surface diseases.