This study’s objective was to determine the prevalence of TB among mentally ill patients in Afghanistan. A cross-sectional study was conducted in five public health facilities and one private facility. All patients in those centers were screened for TB, and the diagnosis of TB was made with GeneXpert or made clinically by a physician. Out of 8,598 patients registered, 8,324 (96.8%) were reached and 8,073 (93.9%) were screened for TB, of whom 1,703 (21.1%) were found to be presumptive TB patients. A total of 275 (16.7%) were diagnosed with all forms of TB, of whom 90.5% were women. The overall prevalence of TB among mentally ill patients was 3,567/100,000—20 times higher than the national incidence rate. TB was independently associated with married and widowed adults, young adults, females, and oral sleep drug users. TB among mentally ill patients is very high, and we recommend that TB care and prevention services be integrated into mental health centers.