Background: Depression among older adults with cancer is under recognized and under treated. This study characterizes the burden of depression in older adults with gastrointestinal (GI) malignancies prior to chemotherapy and its relationship with geriatric assessment (GA) domains, health-related quality of life (HRQOL), and self-reported healthcare utilization. Methods: Patients ≥60 years in GI oncology clinics at UAB were asked to complete a GA entitled the Cancer & Aging Resilience Evaluation (CARE). We examined depression using the Patient-Reported Outcomes Measurement Information System (PROMIS®) Depression four-item short form; moderate/severe depression was defined by a t-score ≥ 60. Multivariate analysis was used to examine associations between those with and without moderate/severe depression. Results: Of 355 included patients, 46 had mild depression (13%) and an additional 46 patients had moderate/severe depression (13%). After adjustment for age, sex, education, cancer type, and cancer stage, those who reported moderate/severe depression had a significantly increased odds of reporting falls (adjusted odds ratio [aOR] 4.01, 95% confidence interval [CI] 1.94–8.26), dependence in IADLs (aOR 7.06,CI 2.91–17.1), dependence in ADLs (aOR 6.23, CI 2.89–13.4), malnutrition (aOR 5.86, CI 2.40–14.3), frailty (aOR 13.7, CI 5.80–32.1), and fatigue (aOR 11.2, CI 3.31–37.6). Moderate/severe depression was also significantly associated with worse physical (aOR 7.58, CI 3.30–17.4) and mental (aOR 26.3, CI 10.1–68.8) HRQOL sub-scores, without significant differences in healthcare utilization. Conclusions: More than one out of eight older adults with a GI malignancy reported moderate/severe depression prior to chemotherapy, which was associated with impairments in several GA domains and HRQOL.