%X Pesticides have underpinned significant improvements in global food security, albeit with associated environmental costs. Currently, the yield benefits of pesticides are threatened as overuse has led to wide-scale evolution of resistance. Despite this threat, there are no large-scale estimates of crop yield losses or economic costs due to resistance. Here, we combine national-scale density and resistance data for the weed Alopecurus myosuroides (black-grass) with crop yield maps and an economic model to estimate resistance impacts. We estimate that the annual cost of resistance in England is £0.4 billion in lost gross profit (2014 prices) and annual wheat yield loss due to resistance is 0.8 million tonnes. A total loss of herbicide control against black-grass would cost £1 billion and 3.4 million tonnes of lost wheat yield annually. Worldwide, there are 253 herbicide-resistant weeds, so the global impact of resistance could be enormous. Our research supports urgent national-scale planning to combat resistance and an incentive for increasing yields through food-production systems rather than herbicides. %A A Varah %A K Ahodo %A S Coutts %A H Hicks %A D Comont %A L Crook %A R Hull %A P Neve %A D Childs %A P Freckleton %A K Norris %V 3 %J Nature Sustainability %D 2020 %L discovery10086408 %P 63-71 %T The costs of human-induced evolution in an agricultural system %O This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.