Background: Suicide is among the leading causes of death for college students. We aimed to assess the impact of the pandemic on trends in suicidal thoughts and behaviors among college students, and whether suicidal thoughts and behaviors were associated with COVID-19 infection and psychosocial factors. Methods: We analyzed 2017–2021 data from 4 waves of Healthy Minds Study including a random sample of college students (N = 354,473) from 286 U.S. institutions. We performed interrupted time series analysis to model the effect of the pandemic on trends in suicidal ideation (SI), plan (SP), and attempt (SA). At the peripandemic assessment, we utilized multivariable logistic regression to examine the association of SI, SP, and SA with COVID-19 infection and psychosocial factors. Results: We observed significant decreases in SI, SP, and SA among college students from 2017 to 2021. The pandemic was significantly associated with a 1.33 percentage points reduction in SI and a 0.85 percentage points reduction in SP but was not associated with a significant reduction in SA. Adjusted associations of SI, SP, and SA with risk factors showed the significant odds ratio (OR) for suspected COVID-19 infection (SI: 1.33, SP: 1.22, SA: 1.32), severe depression (SI: 6.39, SP: 6.63, SA: 5.63), severe anxiety (SI: 3.66, SP: 3.62, SA: 3.60), COVID-19-related financial stress (SI: 1.35, SP: 1.34, SA: 1.48), food insecurity (SI: 2.12, SP: 2.13, SA: 2.79), and academic impairment (SI: 2.07, SP: 2.05, SA: 2.14) but not for test-confirmed COVID-19. Conclusion: Certain COVID-19 mitigation strategies might have protected college students from suicidal thoughts/behaviors.