An optimal spatio-temporal hybrid model (STHM) based on wavelet transform (WT) is proposed to improve the sensitivity and accuracy of detecting slowly evolving faults that occur in the early stage and easily submerge with noise in complex industrial production systems. Specifically, a WT is performed to denoise the original data, thus reducing the influence of background noise. Then, a principal component analysis (PCA) and the sliding window algorithm are used to acquire the nearest neighbors in both spatial and time dimensions. Subsequently, the cumulative sum (CUSUM) and the mahalanobis distance (MD) are used to reconstruct the hybrid statistic with spatial and temporal sequences. It helps to enhance the correlation between high-frequency temporal dynamics and space and improves fault detection precision. Moreover, the kernel density estimation (KDE) method is used to estimate the upper threshold of the hybrid statistic so as to optimize the fault detection process. Finally, simulations are conducted by applying the WT-based optimal STHM in the early fault detection of the Tennessee Eastman (TE) process, with the aim of proving that the fault detection method proposed has a high fault detection rate (FDR) and a low false alarm rate (FAR), and it can improve both production safety and product quality.