A collection of 253 synthetic hexaploid wheats (SHWs) produced from 192 Aegilops tauschii accessions and 39 elite durum varieties were studied to identify, characterise, and evaluate potentially untapped diversity of disease resistance in wheat. The diseases for which resistance was sought included cereal cyst nematode (CCN), root lesion nematode (RLN), Stagonospora nodorum blotch (SNB), Septoria tritici blotch (STB), and the 3 rusts, leaf rust, stem rust, and stripe rust, all important diseases of bread wheat worldwide, which can severely reduce wheat yield and quality. The SHWs exhibited a wide spectrum of resistance to the 8 pathogens. The frequency of disease-resistant SHWs ranged from 1% for one species of RLN (Pratylenchus neglectus), 3% and 10% for Septoria nodorum leaf and glume blotch, 10% for seedling resistance to yellow leaf spot, 16% for CCN, 21% for the second species of RLN (Pratylenchus thornei), 73% for Septoria tritici blotch, and 15%, 40%, and 24% for leaf rust, stem rust, and stripe rust, respectively. Five SHWs, Aus26860, Aus30258, Aus30294, Aus30301, and Aus30304, exhibited high levels of resistance to CCN, YLP, STB, LR, and SR, while 56 SHWs showed resistance to either 3 or 4 diseases. The genetics of resistance to CCN in some of the SHWs revealed that some of the accessions carry the same CCN gene(s) against pathotype Ha13, while others may carry different resistance gene(s). Additional studies were carried out to understand the relationship between the resistances identified in SHWs and the ones already present in common wheat, in particular the resistance genes Cre1 and Cre3 against CCN. The use of perfect markers associated with Cre1 and Cre3 suggested that some SHWs may carry a new CCN resistance gene(s), which could be deployed in breeding programs to increase the diversity of available resistance. The identification of SHWs with resistance to a range of diseases provides an opportunity to generate genetic knowledge and resistant germplasm to be used in future variety development.