Background and Objectives: Caregiving for geriatric patients is essential for ensuring the well-being and quality of life of older adults. Family caregivers play a crucial role, but they often face a significant burden that can lead to adverse mental health outcomes, including depression. This study aimed to estimate the prevalence of depression among caregivers of geriatric patients in Jeddah, Saudi Arabia, and to analyze its association with caregiver burden and various socio-demographic and caregiving parameters. Methods: A cross-sectional study was conducted in Jeddah, Saudi Arabia, between January and March 2024. Adult caregivers of geriatric patients were recruited through various social media platforms. Data were collected via an electronic questionnaire that included demographic information, caregiving parameters, the Patient Health Questionnaire-9 (PHQ-9) for depression screening, and the Zarit Burden Interview (ZBI-12) for caregiver burden assessment. Data were analyzed using descriptive statistics, chi-square tests, and multivariate logistic regression. Results: Of the 269 participants, the average age was 32 years, and the gender distribution was nearly balanced. The prevalence of depression (PHQ-9 score ≥ 10) among caregivers was 45.4% (95% CI: 39.3, 51.5%). Significant factors associated with higher depression scores included younger age, female gender, single status, being a student, low income, and caregiving burden. In the multivariate analysis, female gender (OR 2.50, 95% CI 1.30–4.80) and caregiving burden (mild-to-moderate burden: OR 6.18, 95% CI 2.94–13.00; high burden: OR 22.75, 95% CI 8.75–59.13) were independent predictors of depression. Conclusions: The study highlights the high prevalence of depression among caregivers of geriatric patients in Jeddah and underscores the significant impact of caregiving burden on mental health. These findings emphasize the need for targeted interventions, such as mental health support, respite care programs, and culturally sensitive educational training, to mitigate caregiver burden and enhance the well-being of caregivers.