Colorectal cancer remains an increasingly common disease with uncommon burden of disease, heterogeneity in manifestation, and no definitive treatment. Against this backdrop, renewed efforts to unravel the genetic drivers of colorectal cancer progression are paramount. Early-stage detection of cancer increases success of treatment as well as prognosis. Here, we have executed a comprehensive computational workflow aimed at uncovering the discrete stagewise genetic drivers of colorectal cancer progression. Using the TCGA COADREAD expression data and clinical metadata, we constructed stage-specific linear models and contrasts to identify stage-specific differentially expressed genes. Stage-specific differentially expressed genes with a significant monotone trend of expression across the stages were identified as progression-significant biomarkers. Among the biomarkers identified are: CRLF1, CALB2 (stage-I specific), GREM2, ADCY5, PLAC2, DMRT3 (stage-II specific), PIGR, SLC26A9 (stage-III specific), GABRD, DLX3, CST6, HOTAIR (stage-IV specific), and CDH3, KRT80, AADACL2, OTOP2, FAM135B, HSP90AB1 (top linear model genes). In particular the study yielded 19 genes that are progression-significant such as CCDC19, SERPINE1, HOXC11, SOX10. The existing literature for many of these biomarkers are discussed and analyzed for encouraging evidence of translational utility that would still need clinical validation. The study yielded many classes of biomarkers, which could serve in signature panels for early-stage colorectal cancer diagnosis as well as establish strategies for therapy. Our work is a concrete step in the direction of establishing the molecular signatures of the discrete progressive stages of colorectal cancer, with the future goal of securing more effective treatment for the condition.