Abstract Future exoplanet direct imaging missions, such as HabEx and LUVOIR, will select target stars to maximize the number of Earth-like exoplanets that can have their atmospheric compositions characterized. Because one of these missions’ aims is to detect biosignatures, they should also consider the expected biosignature yield of planets around these stars. In this work, we develop a method of computing relative biosignature yields among potential target stars, given a model of habitability and biosignature genesis, and using a star’s habitability history. As an illustration and first application of this method, we use MESA stellar models to calculate the time evolution of the habitable zone and examine three simple models for biosignature genesis to calculate the relative biosignature yield for different stars. We find that the relative merits of K stars versus F stars depend sensitively on model choice. In particular, use of the present-day habitable zone as a proxy for biosignature detectability favors young, luminous stars lacking the potential for long-term habitability. Biosignature yields are also sensitive to whether life can arise on Cold Start exoplanets that enter the habitable zone after formation, an open question deserving of more attention. Using the case study of biosignature yields calculated for θ Cygni and 55 Cancri, we find that robust mission design and target selection for HabEx and LUVOIR depend on choosing a specific model of biosignature appearance with time, the terrestrial planet occurrence rate as a function of orbital separation, precise knowledge of stellar properties, and accurate stellar evolutionary histories.