Background: Carcinoembryonic antigen (CEA) is widely used as a tumor marker in colorectal cancer (CRC). This study aimed to evaluate the role of the degree of change in CEA levels during the treatment period and found that the degree of change highly correlated with disease survival and Response Evaluation Criteria in Solid Tumors (RECIST) criteria in evaluating therapy response. Methods: A total of 447 metastatic CRC patients treated with surgery of the primary tumor followed by systemic therapy at a single center from the year 2000 through 2011 were reviewed. The degree of change in CEA levels was expressed as the CEA ratio (post-CEA/pre-CEA) and classified into four groups during the treatment period for further evaluation. The imaging change of the same population was also compared with the CEA ratio during the treatment period. Results: The CEA ratio was significantly correlated with different chemotherapy regimens (p < 0.001), pre-treatment CEA level (p < 0.001), lymphovascular invasion (p = 0.006), and tumor differentiation (p = 0.018). CEA ratio and imaging change according to RECIST criteria were both correlated with overall survival (p < 0.001). These two methods for evaluating treatment response were highly correlated (p < 0.001). Conclusions: CEA ratio was found to be a reliable prognostic factor in stage IV CRC, and was highly correlated with the imaging survey according to RECIST criteria. Further prospective studies are essential to validate these findings.