Increasingly stringent fuel economy and CO2 emission regulations provide a strong impetus for development of high-efficiency engine technologies. Diesel engines dominate the heavy duty market and significant segments of the global light duty market due to their intrinsically higher thermal efficiency compared to spark-ignited (SI) engine counterparts. Predictive simulation tools can significantly reduce the time and cost associated with optimization of engine injection strategies, and enable investigation over a broad operating space unconstrained by availability of prototype hardware. In comparison with 0D/1D and 3D simulations, Quasi-Dimensional (quasi-D) models offer a balance between predictiveness and computational effort, thus making them very suitable for enhancing the fidelity of engine system simulation tools. A most widely used approach for diesel engine applications is a multizone spray and combustion model pioneered by Hiroyasu and his group. It divides diesel spray into packets and tracks fuel evaporation, air entrainment, gas properties, and ignition delay (induction time) individually during the injection and combustion event. However, original submodels are not well suited for modern diesel engines, and the main objective of this work is to develop a multizonal simulation capable of capturing the impact of high-injection pressures and exhaust gas recirculation (EGR). In particular, a new spray tip penetration submodel is developed based on measurements obtained in a high-pressure, high-temperature constant volume combustion vessel for pressures as high as 1450 bar. Next, ignition delay correlation is modified to capture the effect of reduced oxygen concentration in engines with EGR, and an algorithm considering the chemical reaction rate of hydrocarbon–oxygen mixture improves prediction of the heat release rates. Spray and combustion predictions were validated with experiments on a single-cylinder diesel engine with common rail fuel injection, charge boosting, and EGR.