Background: Although studies have examined how depressed patients’ baseline characteristics predict depression course, still needed are studies of how depression course is associated with modifiable long-term outcomes. Aims: This study examined six outcomes of three groups representing distinct depression courses (low baseline severity, rapid decline; moderate baseline severity, rapid decline; and high baseline severity, slow decline): medical functioning, coping patterns, family functioning, social functioning, employment, and work functioning. Method: Adults with depression at baseline (N = 382; 56% women) were followed for 23 years on self-reported outcomes (79% response rate). Data from the baseline assessment and follow-ups (1, 4, 10, and 23 years) were used in a longitudinal analysis to examine associations between depression course and outcomes. Results: All depression course groups declined on medical and social functioning and employment over follow-up. The high- and moderate-severity depression course groups reported poorer coping patterns than the low-severity group. The high-severity depression course group reported poorer family functioning than the moderate-severity group, and had the poorest work functioning outcome, followed by the moderate-severity and then the low-severity groups. Conclusions: Patients with a high- or moderate-severity depression course may benefit from treatment that manages coping patterns and improves family and work functioning.