Introduction. Depression is the most common mental health disorder worldwide with a lifetime prevalence of approximately 10% in the general population. Our objective was to assess the knowledge, attitudes, and practices among healthcare workers (HCWs) regarding depression care. Methods. We conducted a cross-sectional study among consenting healthcare workers in two medium-sized hospitals in Kenya. Data on demographic characteristics, knowledge, attitude, and practice of depression were collected through a self-administered structured questionnaire. The Revised Depression Attitude Questionnaire was incorporated into the questionnaire. Knowledge and attitude scores were computed, where higher scores suggested higher knowledge or more positive attitudes. Descriptive and regression analyses were used to assess associations, and a p value of < 0.05 was considered significant. Results. Among the 316 HCWs approached, 303 (95.9%) consented and were enrolled. Almost two-thirds (64.0%) of the respondents were female, and 58.4% were between 18 and 29 years old. HCWs were categorised into three: nurses, clinicians (doctors/clinical officers), and nonclinicians (other healthcare workers). The median knowledge score among respondents was 9 out of 10. Nonclinicians scored significantly lower (β = −0.5, p < 0.011) on the knowledge score compared to clinicians. Only 9.3% of the respondents strongly agreed or agreed that they were confident in assessing the risk of suicide in patients with depression. The median attitude score among respondents was 65 out of 110. The attitude score was positively associated with the knowledge score (β = 0.78, p = 0.001), and respondents with professional experience of 5-14 years had higher attitude scores compared (β = 1.7, p = 0.023) to those with fewer than 5 years. Among clinicians and nurses, 40.3% reported that they rarely or have never been screened for depression. Conclusions. HCWs demonstrated good knowledge of depression’s symptoms and causes but lacked confidence in pharmacological management, with gaps in regular screening and comprehensive care practices, particularly among nonclinicians and less experienced staff. Focused training for these groups could enhance the early detection and treatment of depressed patients.