Modern spark ignition engines can take advantage of better fuel octane quality either towards improving acceleration performance or fuel economy via an active ignition management system. Higher fuel octane allows for spark timing advance and consequently higher torque output and higher engine efficiency. Additionally, engines can be designed with higher compression ratios if a higher anti-knock quality fuel is used. Due to historical reasons, Research Octane and Motor Octane Numbers are the metrics still used to characterize fuels’ anti-knock quality. These octane indicators correlated well with older engines designed about 20 years ago. But the correlation has drifted considerably in the recent past due to advances in engine infrastructures mainly governed by stringent fuel economy and emission standards. In prior research, the octane response of modern engines seemed to correlate better with RON than MON; however, the impact of octane sensitivity (RON-MON) has not been evaluated in detail. In this study, the aforementioned relationship between engine octane appetite and octane sensitivity was studied in a single cylinder direct injection spark ignition (DISI) engine using six fuels with two levels of RON, each of which had three octane sensitivity levels ranging from 5 to 15. Experiments were conducted under three compression ratios ranging from 9.5 to 11.5. The results show that both higher RON and octane sensitivity have positive impacts on the engine thermal efficiency, with RON being more influential than octane sensitivity. It is also found that the effect of octane sensitivity was more pronounced at lower RON fuels.