Objective With scale‐up of antiretroviral therapy (ART) children, treatment failure and switch to subsequent ART regimens are common. Our objectives were to evaluate switching practices and identify factors associated among children and adolescents failing their first‐line ART. Methods A facility‐based survey study was conducted in a cohort of children living with HIV experiencing virological failure (VF) at the Essos Hospital Centre of Yaounde, Cameroon. Data were collected using a standard questionnaire, and key variables were as follows: (a) VF defined as viral load (VL) > 1000 copies/ml, (b) rate of switch to second‐line and (c) reason(s) for switching ART. Odds ratio (OR) with 95% confidence interval (CI) was used to assess the association between study variables, and P < 0.05 was considered statistically significant. Results A total of 106 children experiencing VF were enrolled: median age was 8 [interquartile range (IQR): 3–15] years; 60.38% were boys and 39.62% were orphans of one/both parents. A proportion of 69% were at the WHO clinical stage III/IV, and 13.21% were experiencing immunological failure (CD4 < 200 cells/mm3). The median duration on first‐line ART was 36 [IQR: 7–157] months prior to detecting VF, and the rate of switch to second‐line ART was 70.75% (75/106). Delay in switching ART after a confirmed VF was 11 [IQR: 7–16] months. After switch to second‐line ART, the median time to achieve undetectable VL (<40 copies/ml) was 14 [IQR: 9–21] months. Multivariate analysis revealed that only children with viral rebound (aOR = 0.09; 95% CI = 0.03–0.24) were less likely to be switched. Of note, being orphaned (aOR = 0.35, CI = 0.11–1.11), biological sex (aOR = 1.77, CI = 0.60–5.29) and immune status (aOR = 0.19, CI = 0.03–1.31, 0.09) had no significant effect on switching to second‐line ART. Conclusion In this paediatric population experiencing VF after about 3–4 years from ART initiation, the majority are switched to second‐line ART after a delay of almost one year. Delayed switch to second‐line was driven essentially by viral rebound, underscoring the need for close viral monitoring.