Parastagonospora nodorum and Pyrenophora tritici-repentis are foliar pathogens of wheat, capable of causing up to 50% yield losses, and reduced grain quantity and quality, by infecting wheat leaves and kernels. The most economical means of disease control has been through the introduction of nuclear resistance genes. Changes in wheat’s nuclear-cytoplasmic (NC) interactions by the introduction of alien cytoplasms, can affect disease resistance. In this study, we investigated 32 alloplasmic lines derived from wheat cultivars Selkirk, Chris, and 56-1 (durum), in response to isolates of P. nodorum, P. tritici-repentis, and four host-specific toxins produced by them. All alloplasmic lines showed no difference from their parental lines with regards to toxin sensitivity. With spore inoculations, alloplasmic lines, SSM0039, SSM0237, and SSM0241, containing either Aegilops bicornis or Ae. longissima cytoplasm, exhibited increased disease resistance, compared to their parental lines. Two lines were found to be resistant to multiple isolates or pathogens.