Heterogeneity in individuals' physiological stress responses is central to theories linking stress with vulnerability to disease. Although multiple cortisol profiles have been reported in response to acute psychological stress, most prior work focuses on a single, average pattern and relative deviations from it, such as greater or lesser response peaks or reactivity. The present aims were to identify cortisol stress response trajectory classes using a data-driven approach and test whether social-evaluative threat (SET), a reliable elicitor of cortisol, predicted a greater likelihood of membership in the more reactive profiles. Data were pooled from 13 acute laboratory stressor studies from two geographically distinct U.S. university communities. Participants included 1,258 adults ranging from 18 to 52 years (Mage = 20.5; 62% women; 38% men) with diverse racial/ethnic identities and socioeconomic statuses. Studies included a version of the Trier Social Stress Test and at least three salivary cortisol assessments. SET was tested in three ways: study conditions with evaluators present, perceptions of evaluation, and ratings of shame-related emotions. Latent group-based trajectory modeling was applied to identify cortisol response patterns that best fit the data. Results revealed five unique cortisol response profiles. Consistent with hypotheses, SET conditions, greater perceived evaluation, and greater shame-related emotions predicted membership in the most reactive response trajectories. The findings highlight the high degree of heterogeneity that characterizes cortisol stress response profiles, which has important implications for theories of stress and health and methodological approaches in future research. (PsycInfo Database Record (c) 2024 APA, all rights reserved).