The auto-ignition characteristics of diethyl ether (DEE)/ethanol mixtures are investigated in compression ignition (CI) engines both numerically and experimentally. While DEE has a higher derived cetane number (DCN) of 139, ethanol exhibits poor ignition characteristics with a DCN of 8. DEE was used as an ignition promoter for the operation of ethanol in a CI engine. Mixtures of DEE and ethanol (DE), i.e., DE75 (75% DEE + 25% ethanol), DE50 (50% DEE + 50% ethanol) and DE25 (25% DEE + 75% ethanol), were tested in a CI engine. While DE75 and DE50 auto-ignited at an inlet air pressure of 1.5 bar, DE25 failed to auto-ignite even at boosted pressure of 2 bar. The peak in-cylinder pressure for diesel and DE75 were comparable, while DE50 showed reduced peak in-cylinder pressure with delayed start of combustion (SOC). Numerical simulations were conducted to study the engine combustion characteristics of DE mixture. A comprehensive detailed chemical kinetic model was created to represent the combustion of DE mixtures. The detailed mechanism was then reduced using standard direct relation graph (DRG-X) method and coupled with 3D CFD code, CONVERGE, to simulate the experimental data. The simulation results showed that the effects of physical properties on DE50 combustion are negligible. Simulations of DE50 mixture revealed that the combustion is nearly homogenous, while diesel (n-heptane used as a surrogate) and DE75 showed similar combustion behavior with flame liftoff and diffusion controlled combustion. Diesel exhibited auto-ignition at an equivalence ratio of 2, while DE75 and DE50 showed auto-ignition in the equivalence ratio range of 1-1.5 and 0-1, respectively. The experiments and numerical simulations demonstrate how the high reactivity of DEE supports the auto-ignition of ethanol, while ethanol acts as a radical scavenger.