Background Growing numbers of people with multimorbidity have a co-occurring mental health condition such as depression. Co-occurring depression is associated with poor patient outcomes and increased healthcare costs including unplanned use of secondary healthcare which may be avoidable. Aim To summarise the current evidence on the association between depression and unplanned secondary healthcare use among patients with multimorbidity. Methods We conducted a systematic review by searching MEDLINE, EMBASE, PsychINFO, Web of Science, CINAHL, and Cochrane Library from January 2000 to March 2021. We included studies on adults with depression and at least one other physical long-term condition that examined risk of emergency hospital admissions as a primary outcome, alongside emergency department visits or emergency readmissions. Studies were assessed for risk of bias using The National Institute of Health National Heart, Lung, and Blood Institute quality assessment tool. Relevant data were extracted from studies and a narrative synthesis of findings produced. Results Twenty observational studies were included in the review. Depression was significantly associated with different outcomes of unplanned secondary healthcare use, across various comorbidities. Among the studies examining these outcomes, depression predicted emergency department visits in 7 out of 9 studies; emergency hospital admissions in 19 out of 20 studies; and emergency readmissions in 4 out of 4 studies. This effect increased with greater severity of depression. Other predictors of unplanned secondary care reported include increased age, being female, and presence of greater numbers of comorbidities. Conclusion Depression predicted increased risk of unplanned secondary healthcare use in individuals with multimorbidity. The literature indicates a research gap in identifying and understanding the impact of complex multimorbidity combinations, and other patient characteristics on unplanned care in patients with depression. Findings indicate the need to improve planned care for patients with moderate-to-severe depression. We suggest regular reviews of care plans, depression severity monitoring and assessment of hospital admission risk in primary care settings.