The exergy loss characteristics of combustion processes under homogeneous-charge compression ignition (HCCI) and stratified-charge compression ignition (SCCI) conditions are numerically investigated by analyzing two-dimensional (2-D) direct numerical simulation (DNS) data. Two fuels, dimethyl ether and ethanol, together with the initial conditions of different mean temperatures, and levels of temperature and concentration fluctuations relevant to HCCI/SCCI conditions were investigated. It is found that the prevalent deflagration mode significantly decreases the maximum exergy loss rates and spreads out the exergy loss rate for all the cases regardless of fuel types, temperature regimes, and temperature and/or concentration fluctuations. The primary irreversible sources of exergy loss are also identified. The chemical reaction is found to be the primary contributor to the total exergy loss, followed by heat conduction and mass diffusion, regardless of the fluctuation levels. It is also found that the relative change of exergy loss due to chemical reactions, ELchemrel, correlates strongly with the heat release fraction by deflagration. The maximum ELchemrel is found to be less than 10%. Chemical pathway analysis reveals that the exergy loss induced by low-temperature reactions, represented by the decomposition of hydroperoxy–alkylperoxy and the H-abstraction reactions of the fuel molecule, is much lower under the SCCI conditions than that under the HCCI conditions. Generally, the dominant reactions contributing to the exergy loss in the high-temperature regime are nearly identical for the HCCI and SCCI combustion. Key reactions, including the H2O2 loop reactions, the reactions of the H2–O2 mechanism, and the conversion reaction of CO to CO2, CO+OH=CO2+H, are found to contribute more than 50% of the total exergy loss. Due to locally higher reactivities by temperature and concentration fluctuations inducing deflagration dominance, these reactions occur at a relatively higher temperature (1600 K–1900 K) compared with the homogeneous zero-dimensional cases (∼1400 K), resulting in a net reduction in exergy loss.