ABSTRACT Ozone is a potential biosignature and disambuguator between Earth-like and Venus-like exoplanets due to its association on Earth with photosynthetically produced oxygen (O$_2$). However, the existence of ozone in Venus’s observable atmosphere, a planet with no known life, raises the possibility of ozone biosignature false-positives on Venus-like exoplanets. We use a photochemical model of Venus’s atmosphere to investigate the origin of its mesospheric ozone layer, and to predict how similar ozone layers would manifest for Venus-like exoplanets. For Venus, our model shows that the previously proposed fluxes of O atoms produced on the dayside and transported to the nightside cannot generate enough ozone to match the observed nightside ozone concentrations without also producing O$_2$ in excess of the observed upper limit. Nor can sufficient ozone be produced by varying the lower-atmosphere chemistry, atmospheric thermal structure, or received stellar flux in our model of Venus’s atmosphere. These results imply that a presently unknown chemical pathway is responsible for the ozone production in Venus’s nightside mesosphere. Ozone production rates from this pathway of 10$^5$–10$^7$ cm$^{-3}$s$^{-1}$ above the cloud layer on the nightside can re-produce the observed O$_3$ concentrations. Generalized to Venus-like exoplanets, known chemistry similarly fails to produce ozone in the abundance seen in the Venusian mesosphere. However, until the origin of Venus’s ozone is understood, we cannot rule out that ozone production at concentrations observable with JWST will be common on abiotic Venus-like worlds, a possibility that limits the usefulness of ozone as a habsignature and as a biosignature.