Background: Academic stress can negatively influence academic performance, particularly in health science programs with high demands. Objective: To analyze the association between perceived academic stress and academic performance in first-year kinesiology students, considering gender differences and stress dimensions (stressors, reactions, and coping strategies). Methods: This cross-sectional study included 82 students assessed using the SISCO-IIA inventory. Academic performance was measured via final course grades. Descriptive analyses, chi-square tests, t-tests, and binary logistic regression models were applied. Results: Students with high levels of academic stressors were significantly more likely to underperform (OR = 4.62, 95% CI [1.24, 17.22], p = 0.023). Female students reported higher emotional and behavioral responses to stress but were less likely to underperform (OR = 0.30, 95% CI [0.11, 0.79], p = 0.014). Age was not significantly associated with performance (p = 0.433). Conclusion: Academic stress negatively influences academic outcomes among first-year students. Gender differences in stress response patterns may affect vulnerability and coping effectiveness. These findings highlight the need for early screening, targeted interventions, and support systems to mitigate academic stress and promote student success.