Stem rust caused by Puccinia graminis f. sp. tritici is one of the most destructive diseases of wheat (Triticum aestivum). In Afghanistan, wheat is an economically important crop, comprising approximately 80% of grain production. Little work has been done to identify Afghan wheat cultivars that are potential sources of stem rust resistance. Five modern Afghan wheat cultivars and 500 wheat accessions from Afghanistan and three adjacent regions in Pakistan, Iran, and Tajikistan were screened at the seedling stage for resistance to stem rust race TPMK. Four of the five modern Afghan cultivars (‘Hazardana’, ‘Kabul-2000’, ‘Solh-02’, and ‘Zardana’) displayed infection type 2 and were considered resistant. The four resistant lines were further evaluated at the Cereal Disease Laboratory (CDL), St. Paul, Minnesota, for resistance to seven stem rust races including TPMK (for confirmation) and TTKS (Ug99). All four lines were susceptible to race TTKS. However, ‘Hazardana’ and ‘Zardana’ were resistant to races QFCS, QTHJ, RCRS, RKQQ, and TTTT. ‘Kabul-2000’ and ‘Solh-02’ were resistant to race QFCS but susceptible to races QTHJ, RCRS, RKQQ, and TTTT. All four cultivars were confirmed at the CDL to be resistant to race TPMK. The susceptibility to race TPMK in all accessions and in one modern Afghan cultivar and the susceptibility to race TTKS in all four cultivars that were resistant to race TPMK indicate a high vulnerability of wheat lines to emerging P. graminis strains both in Afghanistan and adjacent regions.