•Humor styles are linked with well-being even after controlling for shared variance.•Self-enhancing and affiliative humor are linked with lower distress, health problems.•Self-defeating humor is linked with greater health difficulty, distress over time.•Reappraisal and social support are mediators of relations to well-being.•Social competence moderates the relation of aggressive humor with outcomes. Two studies examined relations of humor styles with well-being, social support, cognitive reappraisal, and social competence. In Study 1 (N = 108), self-enhancing and affiliative humor were associated fewer health difficulties and less psychological distress, mediated by reappraisal and social support, respectively. Self-defeating humor was associated with greater distress, mediated by both reappraisal and social support. Social competence moderated the relation of aggressive humor with social support: Individuals high on both aggressive humor and communication difficulties reported the least support. Study 2 followed undergraduates (N = 193) over ten weeks. T1 results for psychological distress replicated Study 1. Social support and reappraisal mediated relations of humor styles with T1 distress, and social support indirectly mediated the relation of aggressive humor with increased T2 distress. Aggressive humor was associated with T1 health difficulties, and self-defeating humor predicted greater health difficulties over time. Reappraisal and social support indirectly mediated the relation of self-enhancing and affiliative humor with fewer T1 health difficulties, and social support indirectly mediated the relation of aggressive humor with increased health difficulties over time. Communication difficulties moderated the relation of aggressive humor with fewer T1 positive interactions and greater somatic symptoms over time. Relations largely held controlling for shared variance among humor styles.