In previous research, there have been more investigations on methanol blended with other fuels such as diesel, biodiesel, gasoline, etc., but fewer investigations on methanol with ignition additives as a mono-fuel. To better understand the methanol mono-fuel combustion characteristics and to further apply them, a combined experimental and simulation study of methanol in a Scania heavy-duty compression ignition (CI) engine was carried out in this work. The experiments consisted of four groups with variable injection timings, variable fraction of ignition additives, variable charge air temperatures, and variable overall excess air ratios/power sweeps. Heat release rate (HRR), cylinder pressure, ignition delay and indicated efficiency were analyzed for each case. The analysis showed that the combustion type was partially premixed combustion (PPC) in some cases and diesel-like combustion in the rest. By observing all cases, the shortest ignition delay was 14.1°, and the longest was 22.8°. The indicated efficiencies were in the range of 0.35 to 0.43. Simulations and validation analyses were performed for all cases by a multi-packets model. The physical and chemical ignition delays were predicted. The physical ignition delays were in the range of 4.25 to 8.10°, and the chemical ignition delays were in the range of 6.66 to 17.1°. The chemical ignition delay was always longer than the physical one. This indicates that chemical ignition delay has to be prioritized to improve the ignition performance of methanol fuel.