Lysine acetylation is an important and ubiquitous posttranslational modification conserved in prokaryotes and eukaryotes. This process, which is dynamically and temporally regulated by histone acetyltransferases and deacetylases, is crucial for numerous essential biological processes such as transcriptional regulation, cellular signaling, and stress response. Since the experimental identification of lysine acetylation sites within proteins is time-consuming and laboratory-intensive, several computational approaches have been developed to identify candidates for experimental validation. In this work, acetylated protein data collected from UniProtKB were categorized into histone or nonhistone proteins. Support vector machines (SVMs) were applied to build predictive models by using amino acid pair composition (AAPC) as a feature in a histone model. We combined BLOSUM62 and AAPC features in a nonhistone model. Furthermore, using maximal dependence decomposition (MDD) clustering can enhance the performance of the model on a fivefold cross-validation evaluation to yield a sensitivity of 0.863, specificity of 0.885, accuracy of 0.880, and MCC of 0.706. Additionally, the proposed method is evaluated using independent test sets resulting in a predictive accuracy of 74%. This indicates that the performance of our method is comparable with that of other acetylation prediction methods.