Despite large numbers of patients accessing antiretroviral treatment (ART) in Kenya, few studies have explored factors associated with virologic failure in Western Kenya, specifically. We undertook a study in Homa Bay County, Kenya to assess the extent of virologic treatment failure and factors associated with it. This was an observational retrospective study conducted from September 2020 to January 2021. Data were abstracted from the records of patients who had been on ART for at least six months at the time of data collection after systematic sampling stratified by age group at ART initiation (0–14 and 15+ years), using probability proportion to the numbers of patients attending the facility. Confirmed viral treatment failure was defined as viral load ≥1000 copies/ml based on two consecutive viral load measurements after at least three months of enhanced adherence counseling. Data were analyzed using descriptive statistics and Cox regression modeling. Of the 2,007 patients sampled, 160 (8.0%) had confirmed virologic treatment failure. Significantly higher virologic treatment failure rates were identified among male patients 78/830 (9.4%) and children 115/782 (14.7%). Factors associated with virologic treatment failure (VTF), were age 0–14 years, adjusted hazard ratio (AHR) 4.42, (95% Confidence Interval [CI], 3.12, 6.32), experience of treatment side effects AHD: 2.43, (95% CI, 1.76, 3.37), attending level 2/3 health facility, AHR: 1.87, (95% CI: 1.29, 2,72), and history of opportunistic infections (OIs), AHR: 1.81, (95% CI, 1.76, 3.37). Children, attendees of level 2/3 health facilities, patients with a history of OIs, and those experiencing treatment side-effects are at risk of VTF. Increased focus on children and adolescents on screening for drug resistance, administration of and adherence to medication, and on effective information and education on side-effects is critical. Additionally, there is need for increased training and support for health care workers at primary level care facilities.