We present gas-aerosol and aqueous phase chemical wave systems for novel safeguards sensing and in situ logic-tree analysis. Chemical waves are self-sustaining fluctuations in chemical concentrations that arise from nonlinear coupling of transport and chemical reactions in a fluid medium. Chemical waves respond to and retain a history of encountered stimuli, and the waves propagate spatially even in the absence of advection. Key attributes for safeguards sensing include the filling of space in difficult-to-access systems and transmission of information by diagnostic wave trains (i.e., information-containing pulses or changes in chemical concentrations that are analogous to telegraph signals). Amplitude and frequency of chemical waves can be tuned in sensitivity to indicate the presence of targeted products or signatures. Chemical waves can be triggered by trace quantities of solid, gaseous, or liquid chemical compounds, physico-acoustic perturbations, radiation, magnetic fields, and optical/UV stimulation. We use computational fluid dynamics modeling coupled to chemical reactions to demonstrate sensing scenarios, including: ozone-aerosol autocatalysis for identifying and transmitting evidence of breaches or other safeguards triggers in tightly packed dry-cask storage of spent fuel; and unauthorized intrusion detection in a subsurface geologic repository for nuclear waste via gas- or liquid-phase chemical waves in repository galleries and/or engineered and natural barrier systems. Laser, absorption, and vibrational spectroscopy are proposed for read out of chemical wave trains. Logic-tree analysis represents interrelated and cascading yes/no questions (Boolean operations) of a safeguards inspection. By careful design and tuning, the chemical wave system spatially spreads and seeks out safeguards triggers, responds in a yes/no manner as a chemical circuit, and transmits results back to the inspectorate, thereby performing an in situ logic-tree analysis. Sandia National Laboratories is a multimission laboratory managed and operated by National Technology & Engineering Solutions of Sandia, LLC, a wholly owned subsidiary of Honeywell International Inc., for the U.S. Department of Energy’s National Nuclear Security Administration under contract DE-NA0003525.