Delays in development that occur during early childhood can have long-lasting consequences, potentially leading to poor academic achievement. Research has shown that the human immunodeficiency virus can have neurotropic effects, which may impact the development of the brain in infected children. However, there is a scarcity of evidence regarding developmental delays among children with human immunodeficiency virus in the study area. This study aimed to determine the prevalence of developmental delay and associated factors among children with the human immunodeficiency virus in southern Ethiopia. A cross-sectional study was undertaken among 422 children aged below five during October 30 to December 30, 2021, who acquired the human immunodeficiency virus at public hospitals. A pretested tool anthropometric measurements were utilized. To examine developmental delay, the age and stage questionnaires (version 3) were used. Descriptive statistics were performed. Bivariable and multivariable binary logistic regression models were fitted to identify potential factors associated with delays in child development. The analysis was performed using STATA version 14.2. Adjusted odds ratios with 95% confidence intervals and variables with p-values less than 0.05 were considered to be significantly associated with global developmental delay. A total of 413 under-five children with human immune virus participated, with a 97.9% response rate. Of all children, 222 (53.75%) were male, and the mean age of children was 3.5 ± 1 (± SD) years. Overall global developmental delay was 41.89% [95% CI 37-47%]. Maternal age 35 and older [AOR 2.2; 95% CI (1.11-4.3)], maternal educational status [AOR 0.47; 95% CI (0.23-0.96)], higher birth order [AOR 3; 95% CI (1.5-4)], and stunting [AOR 2.2; 95% CI (1.4-3.42)] were significant factors associated with global developmental delay. Half of the children examined demonstrated delayed development across domains. The global developmental delay constitutes a significant public health concern, underscoring the necessity for early detection initiatives including developmental screening, diagnostic evaluations, and therapeutic interventions. We found significant associations between the developmental status of the children and the maternal age, educational level of mothers, higher birth order, and stunting of under-five children. Policies should aim to enhance mother and child health services, expand access to early intervention programs, and incorporate developmental surveillance into routine pediatric care. Additional research may be necessary to elucidate the underlying causes of the high prevalence of Global developmental delay, evaluate the efficacy of current interventions, and investigate innovative approaches to mitigate developmental delays.