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Rapid tests have the potential to improve the identification of HIV-infected children in resource-limited settings. However, they remain underutilized because of a lack of data on their performance in the field using whole blood specimens. This study aimed to assess the accuracy of rapid tests for detecting HIV exposure, excluding HIV infection in HIV-exposed infants, and diagnosing HIV infection in children older than 18 months of age.Five rapid tests (First Response, Pareekshak, Determine, Smart Check, and Insti) were performed using whole blood from children enrolled in a multisite, cross-sectional study in South Africa. HIV enzyme-linked immunosorbent assay and DNA polymerase chain reaction results defined HIV exposure and infection, respectively, and were the standards used for comparison.Of the 851 children enrolled, 186 (21.9%) were infected with HIV. For detecting HIV exposure, Determine demonstrated the highest sensitivity of 99.3% (95% confidence interval, 98.0–99.8) in early infancy, but sensitivity declined with age as seroreversion occurred. After 8 months of age, all tests except First Response excluded HIV infection in 82% to 100% of HIV-uninfected infants and, in conjunction with a clinical assessment, did not miss any HIV-infected children. Insti was the only test that detected all HIV-infected infants, albeit on the smallest number of samples. The performance of all rapid tests in children older than 18 months of age was similar to that in adults.Determine was the only rapid test that had a high enough sensitivity for detecting HIV exposure in early infancy, but it identified seroreversion later in life than the other tests. Insti warrants further investigation for both indications.