A total of 12 QTL conferring resistance to tan spot induced by a race 2 isolate, 86-124, were identified in three tetraploid wheat mapping populations. Durum is a tetraploid species of wheat and an important food crop. Tan spot, caused by the necrotrophic fungal pathogen Pyrenophora tritici-repentis (Ptr), is a major foliar disease of both tetraploid durum wheat and hexaploid bread wheat. Understanding the Ptr-wheat interaction and identifying major QTL can facilitate the development of resistant cultivars and effectively mitigate the negative effect of this disease. Over 100 QTL have already been discovered in hexaploid bread wheat, whereas few mapping studies have been conducted in durum wheat. Utilizing resistant resources and identifying novel resistant loci in tetraploid wheat will be beneficial for the development of tan spot-resistant durum varieties. In this study, we evaluated four interconnected tetraploid wheat populations for their reactions to the race 2 isolate 86-124, which produces Ptr ToxA. Tsn1, the wheat gene that confers sensitivity to Ptr ToxA, was not associated with tan spot severity in any of the four populations. We found a total of 12 tan spot-resistant QTL among the three mapping populations. The QTL located on chromosomes 3A and 5A were detected in multiple populations and co-localized with race-nonspecific QTL identified in other mapping studies. Together, these QTL can confer high levels of resistance and can be used for the improvement in tan spot resistance in both hexaploid bread and durum wheat breeding. Two QTL on chromosomes 1B and 7A, respectively, were found in one population when inoculated with a ToxA knockout strain 86-124ΔToxA only, indicating that their association with tan spot was induced by other unidentified necrotrophic effectors, but under the absence of Ptr ToxA. In addition to removal of the known dominant susceptibility genes, integrating major race-nonspecific resistance loci like the QTL identified on chromosome 3A and 5A in this study could confer high and stable tan spot resistance in durum wheat.