In contrast to the general stratospheric ozone recovery following international agreements, recent observations show an ongoing net ozone depletion in the tropical lower stratosphere (LS). This depletion is thought to be driven by dynamical transport accelerated by global warming, while chemical processes have been considered to be unimportant. Here we use a chemistry–climate model to demonstrate that halogenated ozone-depleting very short-lived substances (VSLS) chemistry may account for around a quarter of the observed tropical LS negative ozone trend in 1998–2018. VSLS sources include both natural and anthropogenic emissions. Future projections show the persistence of the currently unaccounted for contribution of VSLS to ozone loss throughout the twenty-first century in the tropical LS, the only region of the global stratosphere not projecting an ozone recovery by 2100. Our results show the need for mitigation strategies of anthropogenic VSLS emissions to preserve the present and future ozone layer in low latitudes.