Prior studies have noted several risk and protective factors for school dropout; however, only a few have examined longer-term vulnerabilities alongside temporary risk and protective factors. Consequently, we focused on the role that both stable and time-varying psychosocial risk and protective factors play in dropout intentions and actual dropout, using a 4-year longitudinal design. We investigated to what extent dropout intentions and dropout can be predicted by an interplay between negative life events, general self-efficacy, and perceived social support. We distinguished between time-averaged levels of self-efficacy and social support, and within-person change in self-efficacy and social support over time. This enabled us to establish whether dropout intentions and dropout were sensitive to fluctuations in perceived self-efficacy and social support over time when controlling for person-specific levels of these psychosocial resources. Calculating multilevel models with data from a prospective cohort study (N = 4,956, 43% male), we found that negative life events were significantly associated with an increase in dropout intentions and the likelihood of school dropout. Furthermore, time-averaged levels of self-efficacy and social support, and a within-person (situational) increase in these characteristics relative to their time-averaged levels, were related to lower levels of dropout intentions but did not prevent dropout. The positive relationship between negative life events and dropout intentions was attenuated for individuals who perceived higher levels of self-efficacy than usual. Our findings suggest future research should further investigate time-averaged and situational psychosocial drivers of school dropout in combination.