The recent developments in the sustainable production of n-hexanol, in addition to its distinctive physicochemical properties, have encouraged its application in direct-injection compression-ignition (DICI) engines. However, there has been limited research on the substitution of commercial diesel fuel with n-hexanol in DICI engines. This study investigated the impact of blending ratio of an n-hexanol-diesel mixture (up to 50% v/v) on combustion, performance, and emission characteristics of a DICI engine. A single-cylinder 4-stroke air-cooled naturally aspirated diesel engine was used to conduct these investigations. Blending ratios of 10%, 20%, 30%, 40%, and 50% by volume were used in this study without modifying the fuel system. The experiments were performed for two distinct engine settings, namely, at a speed of 900 rpm at 10% engine load and at a speed of 1500 rpm at four engine loads of 25%, 50%, 75%, and 100%. The results demonstrate that the addition of nhexanol to diesel increased the ignition delay, improved the premixed burn mode, and inhibited the diffusion burn mode. In addition, the total cumulative heat released increased by 9% and 4% for the Hex50 blend (50% nhexanol and 50% diesel) at engine loads of 75% and 100%, respectively. However, the brake thermal efficiency obtained for commercial diesel fuel was 0.6% greater than that of the n-hexanol-diesel blends. The brake-specific fuel consumption of the Hex50 blend at engine load of 100% was 6.4% higher than that of diesel. NOx emissions and smoke opacity reduced by 26% and 54%, respectively, for Hex50 at an engine load of 100%. Thus, n-hexanol can be used with a maximum substitution rate of 50% in the DICI engines, resulting in substantial environmental benefits and negligible technical issues.