Whether fungicide resistance management is optimised by spraying chemicals with different modes of action as a mixture (i.e. simultaneously) or in alternation (i.e. sequentially) has been studied by experimenters and modellers for decades. However results have been inconclusive. We use previously-parameterised and validated mathematical models of wheat septoria leaf blotch and grapevine powdery mildew to test which tactic provides better resistance management, using the total yield before resistance causes disease control to become economically-ineffective (“lifetime yield”) to measure effectiveness. We focus on tactics involving the combination of a low-risk and a high-risk fungicide, and the case in which resistance to the high-risk chemical is complete (i.e. in which there is no partial resistance). Lifetime yield is then optimised by spraying as much low-risk fungicide as is permitted, combined with slightly more high-risk fungicide than needed for acceptable initial disease control, applying these fungicides as a mixture. That mixture rather than alternation gives better performance is invariant to model parameterisation and structure, as well as the pathosystem in question. However if comparison focuses on other metrics, e.g. lifetime yield at full label dose, either mixture or alternation can be optimal. Our work shows how epidemiological principles can explain the evolution of fungicide resistance, and also highlights a theoretical framework to address the question of whether mixture or alternation provides better resistance management. It also demonstrates that precisely how spray tactics are compared must be given careful consideration.