Wheat stripe rust poses a major threat to global food security. Discovery of disease resistance genes from wild relatives enables multigene stacking that could enhance durability. Here, we use map-based cloning and long-read sequencing to isolate two adjacent nucleotide-binding and leucine-rich repeat (NLR) receptors from wild emmer wheat. Using mutagenesis, gene silencing and genetic transformation, we show that the genes TdNLR1 and TdNLR2 oriented head-to-head are both required for YrTD121-mediated stripe rust resistance. TdNLR1 encodes a canonical NLR (CC-NB-ARC-LRR) protein, whereas TdNLR2 encodes an atypical one (NB-ARC-LRR). Both genes lack an integrated domain previously associated with effector perception, representing a unique architecture for paired NLRs in plants. The coiled coil domain of TdNLR1 triggers cell death and self-associates in planta. YrTD121 was present in wild emmer but absent in all other Triticum species examined. Our work sheds light on the function of paired NLRs in conferring disease resistance and facilitates breeding for resistance.