Populations of African ancestry continue to account for a disproportionate burden of the human immunodeficiency virus type 1 (HIV-1) epidemic in the United States. We investigated the effects of human leukocyte antigen (HLA) class I markers in association with virologic and immunologic control of HIV-1 infection among 338 HIV-1 subtype B-infected African Americans in 2 cohorts: Reaching for Excellence in Adolescent Care and Health (REACH) and HIV Epidemiology Research Study (HERS). One-year treatment-free interval measurements of HIV-1 RNA viral loads and CD4(+) T cells were examined both separately and combined to represent 3 categories of HIV-1 disease control (76 controllers, 169 intermediates, and 93 noncontrollers). Certain previously or newly implicated HLA class I alleles (A32, A36, A74, B14, B1510, B3501, B45, B53, B57, Cw04, Cw08, Cw12, and Cw18) were associated with 1 or more of the endpoints in univariate analyses. After multivariable adjustments for other genetic and nongenetic risk factors of HIV-1 progression, the subset of alleles more strongly or consistently associated with HIV-1 disease control included A32, A74, B14, B45, B53, B57, and Cw08. Carriage of infrequent HLA-B but not HLA-A alleles was associated with more favorable disease outcomes. Certain HLA class I associations with control of HIV-1 infection cross the boundaries of race and viral subtype, whereas others appear confined within one or the other of those boundaries.