In Mexico, suicide has become an important public health problem, representing the third leading cause of death in the adolescent population. Suicidal behavior in adolescents is associated with the interaction of complex relationships between personal, interpersonal, and sociocultural factors. Through a quantitative, descriptive, and correlational cross-sectional study, the present study aimed to analyze the prevalence and risk factors associated with suicidal ideation among adolescents from different high schools of the high school system (SEMS) of the University of Guadalajara, in response to the psychosocial impact of the COVID-19 pandemic. A descriptive statistical analysis was carried out on the data obtained from the 3583 students surveyed, followed by a principal component analysis (PCA) to identify closely related social, emotional, and behavioral variables. The PCA yielded eight principal components, which together represent 75.42% of the variance across psychometric tests. A multiple linear regression analysis was used, with a regression value (R2) of 0.4811, indicating that the explanatory model can predict 48.1% of the variability in suicidal ideation, with a statistical significance level of 0.05. According to the studies conducted, 19% (688 students) showed indicators of high suicide risk and 26.8% (960 students) showed moderate risk. Depression, mental health, health-related quality of life, physical and psychological well-being, and mood and emotions are the most influential factors in suicidal ideation.