Background Academic burnout syndrome is a condition characterized by chronic physical and emotional exhaustion arising from prolonged exposure to demanding academic pressures. In dental education, factors such as early clinical responsibilities and the necessity for technical precision in practice may significantly exacerbate the syndrome. Therefore, this study aimed to evaluate the association of academic burnout syndrome with anxiety, stress, depression, and quality of life in Peruvian dentistry students, considering potential confounding variables. Methods This cross-sectional analytical study, conducted on 566 Peruvian dentistry students, used the Maslach Burnout Inventory (Student-Survey) (MBI-SS) to assess emotional exhaustion, academic inefficacy, and cynicism. The DASS-21 scale was used to diagnose anxiety, stress, and depression, while the EQ-5D test was employed to determine quality of life. The confounding variables considered included age, sex, year of study, marital status, and place of origin. A Poisson regression model with robust variance was used for multivariable analysis, employing adjusted prevalence ratios (APR). Statistical significance was set at p < 0.05. Results Dentistry students with depression and stress had a 35% (APR = 0.65, 95% CI: 0.54-0.78) and 23% (APR = 0.77, 95% CI: 0.63-0.94) lower probability of experiencing academic inefficacy, respectively. Likewise, students with anxiety had a 23% (APR = 0.77, 95% CI: 0.63-0.95) lower probability of experiencing emotional exhaustion, whereas students with depression and stress had 3.7 times (APR = 3.72, 95% CI: 2.12-6.53) and 59% (APR = 1.59, 95% CI: 1.06-2.40) higher probability of exhibiting cynicism, respectively. Additionally, quality of life did not significantly influence emotional exhaustion, depersonalization, or personal accomplishment. Furthermore, compared to fifth-year students, first-year students had a 54% higher probability of experiencing academic inefficacy (APR = 1.54, 95% CI: 1.23-1.92). In addition, first-year students, along with third- and fourth-year students, had an 80% (APR = 0.20, 95% CI: 1.23-1.92), 56% (APR = 0.44, 95% CI: 0.26-0.75), and 63% (APR = 0.37, 95% CI: 0.20-0.69) lower probability of exhibiting cynicism, respectively. Lastly, female students had a 38% (APR = 0.62, 95% CI: 0.43-0.89) lower probability of exhibiting cynicism than male students. Conclusion The findings underscore the multifaceted nature of academic burnout in dental education. While depression and stress were associated with reduced academic inefficacy and cynicism, their adverse clinical implications warrant cautious interpretation. Anxiety was inversely associated with emotional exhaustion, whereas quality of life showed no significant protective role. These results emphasize the necessity of adopting multidimensional strategies to address academic burnout, with interventions tailored to specific academic stages-particularly targeting first-year students-and sex-specific approaches to reduce risk in vulnerable subgroups.