This study examined the contributions of a polymorphism of the corticotropin-releasing hormone receptor type I (CRHR1) gene (rs110402) and a history of child maltreatment—alone and in interaction—to patterns of cortisol reactivity in adolescents. Adolescents between the age of 13 and 17 years with (n = 61) and without (n = 97) a history of child maltreatment were exposed to the Trier Social Stress Test (TSST). Salivary cortisol was assessed at baseline, and 15 and 30 minutes after the start of the speech portion of the TSST. Saliva samples for genotyping rs110402 also were collected. Adolescents with one or more G alleles of rs110402, relative to A allele homozygotes, and those exposed to maltreatment, relative to non-exposed adolescents, exhibited blunted cortisol reactivity to the TSST (although these associations approached, but did not reach, the level of statistical significance when accounting for underlying population structure in our racially and ethnically diverse sample). There was also a trend for a stronger child maltreatment association with cortisol hypo-reactivity among G allele carriers, but this association was not statistically significant. Findings suggest that CRHR1 variation may moderate the downstream effects of child maltreatment on HPA axis function, and implications for understanding mechanisms of risk associated with early adversity are discussed.