The effects of the temporal and spatial distributions of ignition timings of combustion zones on combustion noise in a Direct Injection Compression Ignition (DICI) engine were studied using experimental tests and numerical simulations. The experiments were performed with different fuel injection strategies on a heavy-duty diesel engine. Cylinder pressure was measured with the sampling intervals of 0.1°CA in order to resolve noise components. The simulations were performed using the KIVA-3V code with detailed chemistry to analyze the in-cylinder ignition and combustion processes. The experimental results show that optimal sequential ignition and spatial distribution of combustion zones can be realized by adopting a two-stage injection strategy in which the proportion of the pilot injection fuel and the timings of the injections can be used to control the combustion process, thus resulting in simultaneously higher thermal efficiency and lower noise emissions. Simulated results show that if a large amount of the combustion occurs near the liner walls of the combustion chamber, this significantly contributes to high amplitude pressure oscillations, which leads to heavy knock and low thermal efficiency. Therefore, a well-organized combustion process would be one in which low temperature combustion occurs in the wall regions and subsequently high temperature combustion occurs at the central regions of the chamber, resulting in higher thermal efficiency and lower noise emissions.