Accurate and timely misfire fault diagnosis is of vital significance for diesel engines. However, existing algorithms are prone to fall into model over-fitting and adopt low energy-concentrated features. This paper presents a novel extreme gradient boosting-based misfire fault diagnosis approach utilizing the high-accuracy time–frequency information of vibration signals. First, diesel engine misfire tests were conducted under different spindle speeds, and the corresponding vibration signals were acquired via a triaxial accelerometer. The time-domain features of signals were extracted by using a time-domain statistics method, while the high-accuracy time–frequency domain features were obtained via the high-resolution multisynchrosqueezing transform. Thereafter, considering the nonlinearity and high dimensionality of the original characteristic data sets, the locally linear embedding method was employed for feature dimensionality reduction. Eventually, to avoid model overfitting, the extreme gradient boosting algorithm was utilized for diesel engine misfire fault diagnosis. Experiments under different spindle speeds and comprehensive comparisons with other evaluation methods were conducted to demonstrate the effectiveness of the proposed extreme gradient boosting-based misfire diagnosis method. The results verify that the highest classification accuracy of the proposed extreme gradient boosting-based algorithm is up to 99.93%. Simultaneously, the classification accuracy of the presented approach is approximately 24.63% higher on average than those of algorithms that use wavelet packet-based features. Moreover, it is shown that it obtains the minimum root mean squared error and can effectively prevent the model from falling into overfitting.