Depression is common in adults experiencing homelessness. It is unclear whether continued homelessness is associated with more depressive symptoms. To examine the association between residential status and depressive symptoms in adults aged 50 years or older experiencing homelessness at study entry. This cohort study analyzed results from the Health Outcomes of People Experiencing Homelessness in Older Middle Age (HOPE HOME) project, which in 2013 began enrolling adults aged 50 years or older experiencing homelessness in Oakland, California, and conducted structured interviews every 6 months for a mean duration of 5.5 years through 2023 (for this cohort study). Eligible participants included those aged 50 years or older, able to speak English, and experiencing homelessness at enrollment. We analyzed data collected from 2013 to 2023. The exposure of interest was residential status. At follow-up visits, residential status was categorized as (1) homelessness (meeting the HEARTH [Homeless Emergency Assistance and Rapid Transition to Housing] Act definition) or (2) housed (living in a noninstitutional environment and not meeting the HEARTH Act definition). The primary outcome was moderate to severe depressive symptoms (with Center for Epidemiologic Studies-Depression [CES-D] scale score ≥22). The augmented inverse probability of treatment weighting (AIPTW) approach was used to examine the association between continued homelessness and depressive symptoms. The AIPTW adjusted for the following variables: number of chronic health conditions, age, sex, visiting a health care practitioner, receiving outpatient mental health treatment, receiving mental health medication, exposure to abuse, substance use disorder, and binge drinking. The cohort was composed of 450 participants, of whom 343 (76.2%) were males, and the mean (SD) age was 58.5 (5.2) years. Participants completed a median (IQR) of 8.9 (8-11) follow-up visits. With 1640 person-years of observation time, participants continued homelessness for 880 person-years (57.1%) and experienced being housed for 715 person-years (44.3%). Many participants (304 [78.0%]) were housed during at least 1 follow-up visit. The odds of a CES-D scale score of 22 or higher was significantly higher among participants who continued experiencing homelessness than among housed participants (marginal causal odds ratio, 1.08; 95% CI, 1.04-1.11; P < .001). This cohort study found that continued homelessness was associated independently with increased odds of depressive symptoms. Obtaining housing may have a favorable role in depression and overall well-being of older adults experiencing homelessness and may be considered as a mental health intervention.