A computationally efficient, physics-based model is developed to account for the heat loss that occurs during the compression process and delay period in rapid compression machine (RCM) experiments. The model is formulated using multiple zones (MZs) and accounts for conductive losses in the main reaction chamber as well as convective losses in the piston crevice and ringpack regions. Blowby past the piston ringpack is also considered. The loss terms can be incorporated into the widely-utilized ‘adiabatic core’ model in order to perform ‘volumetric expansion’ calculations during chemical kinetic simulations that correct for pressure and temperature reductions resulting from these energy losses. An advantage of this approach over existing models and ‘ad-hoc’, or empirical methods is that the MZM constants are only a function of the machine geometry and therefore do not vary from experiment to experiment. As such, fewer experiments need to be conducted (e.g., non-reacting tests + reacting tests at each condition), while existing literature data can be more reliably utilized for kinetic model validation and improvement. This formulation also has the potential to account for effects of multi-stage ignition, as well as phase change that can occur during experiments with involatile, transportation-relevant fuels. The performance of the new MZM is validated here via comparisons with multi-dimensional RCM simulations as well as experiments employing non-reacting and reacting mixtures. Excellent agreement is demonstrated for the overall pressure decay experienced in the reaction chamber during the delay period, as well as the computed gas temperature and velocity behavior within the crevice. Predicted thermal stratification within the reaction chamber also agrees well when high pressure, low viscosity conditions are utilized, i.e., when no vorticular motion is present. Computed ignition delay times for H2/O2/diluent mixtures using the new model agree favorably with the reactive CFD simulations and experimental measurements.