Alternaria leaf spot of cotton is a widespread foliar disease worldwide; however, information regarding disease progress and cultivar response under field conditions in northern Argentina is limited. This study aimed to evaluate disease progress, commercial cultivar performance, and the effects of fungicide application on plant growth, yield, and fiber quality. Field experiments were conducted during two growing seasons (2021–22 and 2022–23) in Reconquista, Santa Fe, Argentina, using three commercial upland cotton cultivars grown under fungicide-treated and untreated conditions, under high plant density and narrow row system. A commercial mixture of pyraclostrobin and epoxiconazole was applied at 50, 70, and 100 days after sowing. Disease incidence and severity were assessed over time, and plant growth, yield, and fiber quality traits were evaluated. Disease showed clear temporal progression in both growing seasons, reaching 100% incidence at 110 days after sowing, however, mean severity values remained moderate (<10%). The fungicide neither reduced incidence or severity nor improved yield or fiber quality. However, fungicide-treated plots showed significantly higher aboveground biomass, nearly 20% over control, suggesting a physiological effect unrelated to disease suppression, which warrant further research. Despite low disease pressure, cultivars differed in their response to infection, with NuOpal showing the highest susceptibility and Guazuncho 4 the lowest disease accumulation. Alternaria leaf spot of cotton progresses in northern Argentina even under unfavorable environmental conditions for fungal epidemics. Significant and consistent differences among cultivars were detected across seasons. Under low disease pressure observed in both seasons evaluated, fungicide applications did not significantly affect disease severity, yield or fiber quality.