The current article presents a model wherein reinforcement sensitivity predicts depression and anxiety via trait preferences for concomitant emotion regulation strategies. In Study 1 (N = 593), BAS sensitivity positively predicted reappraisal and BIS sensitivity negatively predicted it. Reappraisal then negatively predicted depression. BIS sensitivity also predicted rumination, which predicted both depression and anxiety. Study 2a confirmed the model developed in Study 1 with an independent sample (N = 513) and examined the relationships longitudinally. While the cross-sectional relationships were generally maintained, reinforcement sensitivity did not predict reappraisal. In Study 2b, participants (N = 218) were assessed a third time one year later, at the onset of the COVID-19 pandemic. During this stressful time, BAS sensitivity did longitudinally predict reappraisal. These studies highlight the role of emotion regulation in mediating the relationship between reinforcement sensitivity and affective pathology, particularly during times of high stress.