Epigenetic modifications function as central controllers of gene expression in cancer, coordinating crucial cellular activities that trigger the initiation and progression of the tumor, besides their importance in therapeutic response. These modifications can control the gene expression without changing the sequence of DNA. In colorectal cancer (CRC), these alterations involving DNA methylation, histone modifications, chromatin rearrangement, and noncoding ribonucleic acids play a significant role in the pathogenesis of CRC. Abnormal DNA methylation silences the tumor suppressor genes, meanwhile leading to the instability of the genome via reduction of the whole methylation. Specific methylation signatures, such as CpG islands, help in categorizing the subtypes of the tumor and predicting the clinical outcomes. In addition, histone-modifying enzymes, including enhancer of zeste homolog 2 and histone deacetylases, are frequently uncontrolled in cancer, leading to alterations in gene expression. Moreover, small regulatory ribonucleic acids such as microRNA-21 and microRNA-143 contribute to the complex networks that regulate cell survival and growth. Collectively, these epigenetic alterations trigger the transition from benign growth to malignant cancer by continuously suppressing crucial genes. Furthermore, the epigenetic markers can be detected in blood and stool specimens, offering promising tools for the early detection of cancer. The major obstacle in cancer treatment is the resistance to chemotherapy drugs, which is mainly caused by epigenetic modifications in cancer cells. Therefore, the new therapeutic ways target the modifications that occur in DNA methylation and histone, mostly in conjunction with conventional therapies. As the metabolites produced by the gut microbiome can alter the host epigenetics, they can promote cancer development. Promising technologies help in the concise proofreading of epigenetic marks, and advanced single-cell analysis is paving the way for personalized treatment approaches. This cutting-edge knowledge of epigenetic regulation mechanisms offers new prospects for enhancing diagnosis, prognosis, and targeted therapies in colorectal cancer.