Remodelling plant immune receptors has become a vital strategy for creating new disease resistance traits to combat the growing threat of plant pathogens to global food security and environmental sustainability. However, current methods are constrained by the rapid evolution of plant pathogens and often lack broad-spectrum and durable protection. Here we report an innovative strategy to engineer broad-spectrum, durable and complete disease resistance in plants through expression of a chime- ric protein containing a flexible polypeptide coupled with a single or dual conserved pathogen-originated protease cleavage site fused in frame to the N terminus of an autoactive nucleotide-binding and leucine-rich-re- peat immune receptor (NLR) containing a coiled-coil or RESISTANCE TO POWDERY MILDEW 8-like coiled-coil domain. Following invasion, patho- gen-originated specific proteases cleave the inactive chimeric protein to form free autoactive NLR, triggering broad-spectrum plant disease resis- tance. We demonstrate that a single engineered NLR can confer broad-spectrum and complete resistance against multiple potyviruses. Given that many pathogenic organisms across kingdoms encode proteas- es, this strategy has the potential to be exploited to control viruses, bacte- ria, oomycetes, fungi, nematodes and pests in plants.