Positivity bounds—the consequences of requiring a unitary, causal, local UV completion—place strong restrictions on theories of dark energy and/or modified gravity. We derive and investigate such bounds for Horndeski scalar-tensor theories and for the first time pair these bounds with a cosmological parameter estimation analysis, using CMB, redshift space distortion, matter power spectrum, and baryon acoustic oscillation measurements from the Planck, SDSS/BOSS, and 6dF surveys. Using positivity bounds as theoretical priors, we show that their inclusion in the parameter estimation significantly improves the constraints on dark energy/modified gravity parameters. Considering as an example a specific class of models, which are particularly well-suited to illustrate the constraining power of positivity bounds, we find that these bounds eliminate over 60% of the previously allowed parameter space. We also discuss how combining positivity requirements with additional theoretical priors has the potential to further tighten these constraints: for instance, also requiring a subluminal speed of gravitational waves eliminates all but ≲1% of the previously allowed parameter space.