Experimental and numerical investigations on the effects of fuel properties on combustion and soot emissions under both conventional and premixed low-temperature combustion (LTC) conditions have been conducted. Three different fuels, diesel, gasoline, and n-butanol, were used to formulate five fuels with different fuel properties. Computational fluid dynamic (CFD) simulations were conducted to predict the combustion processes and soot emissions of the various fuels. The results show that under both conventional and premixed combustion conditions, the cetane number (CN) has the dominant effect on the ignition delay; the volatility, aromatic, and oxygen contents only have a minor influence on ignition delay. High CN fuels need much higher exhaust gas recirculation (EGR) to provide a sufficiently long ignition delay compared to the fuels with lower CN. As a result, the carbon monoxide (CO) and unburned hydrocarbon (UHC) emissions of the high CN fuels are higher than the low CN fuels due to the lower intake oxygen concentrations. The volatility can be important under high, mixing-controlled, conventional combustion conditions, and the high volatility and oxygen content are also beneficial for CO and UHC reduction under high EGR premixed LTC conditions. The CN plays a dominant role in soot emissions, followed by the oxygen content and the volatility under low oxygen concentration conditions. The experiments show that the trade-off between NOx and soot can be totally eliminated by optimizing the diesel/gasoline/butanol blended fuel. A reduced primary reference fuel (PRF)-n-butanol-polycyclic aromatic hydrocarbon (PAH) mechanism was formulated to predict the combustion and soot emissions of the tested fuels, and the effects of fuel chemistry properties on the combustion processes and soot emissions were well predicted. The simulation results show that the mixing process can be greatly improved by adjusting the fuel chemistry properties, which leads to improved combustion and low soot emissions.