Previous studies show that satisfactory engine performance can be achieved by using both the reactivity stratification combustion (RSC) and the concentration stratification combustion (CSC) fueled with n-butanol. However, the different ignition and combustion characteristics between RSC and CSC have not been well explored yet. In this study, the n-butanol/diesel RSC and n-butanol CSC strategies were compared by integrating the KIVA-3V code and the non-dominated sort genetic algorithm II (NSGA-II). For both RCS and CSC, n-butanol was premixed in the initial port. However, diesel and n-butanol were injected into the cylinder for RSC and CSC, respectively. Five important operating parameters were selected as the variables for optimization, including premixed fraction (PF), start of injection (SOI), the initial in-cylinder pressure at the initial valve close (IVC) timing, the initial in-cylinder temperature at the IVC timing (T-ivc), and exhaust gas recirculation (EGR) rate. The optimization results show that, for the realization of the clean and high-efficiency combustion, a wide range of SOI and the high PF are introduced in RSC, whereas a wide range of PF and the early SOI are employed in CSC. Due to the lower reactivity of n-butanol than diesel, CSC requires the higher Tivc than RSC. As a fixed EGR rate, the optimal operating range of the initial temperature is restricted in a narrow range, especially for CSC. The optimal operating range of SOI and PF of RSC is larger than that of CSC. In RSC, the homogeneous charge compression ignition (HCCI)-like combustion shows the lowest fuel consumption and NOx emissions, and the highest ringing intensity (RI). The reactivity control compression ignition (RCCI) combustion demonstrates the overall balanced engine performance. The benefit of the diesel induced ignition combustion on RI is evident, but the high NOx emissions are still a challenge. For CSC, the optimal case with the low concentration stratification of n-butanol achieves the good EISFC, the low NOx emissions, and the high RI. Generally, the RSC strategy is superior to the CSC strategy in terms of the control of combustion phasing, fuel efficiency, and emissions.