Background: Cancer-related fatigue (CRF) is a common and burdensome symptom in cancer patients that is influenced by multiple factors. Identifying factors associated with CRF may help in developing tailored interventions for fatigue management. This study aimed to examine the correlates of CRF among colorectal cancer patients undergoing postoperative adjuvant therapy based on the theory of unpleasant symptoms. Methods: A cross-sectional study was implemented, and finally, a sample of 363 participants from one tertiary general hospital and one tertiary cancer hospital was purposively recruited. Data were collected using the general information questionnaire, cancer fatigue scale, the distress disclosure index, Herth hope index, and perceived social support scale. Univariate analysis and multiple linear regression analysis were performed to determine the correlates of CRF. Results: The mean score of CRF among colorectal cancer patients was 21.61 (SD = 6.16, 95% CI 20.98–22.25), and the fatigue degree rating was “moderate”. The multiple linear regression model revealed that 49.1% of the variance in CRF was explained by hope, sleep disorder, internal family support, self-disclosure, pain, and time since operation. Conclusions: Our study identified several significant, modifiable factors (self-disclosure, hope, internal family support, pain, and sleep disorder) associated with CRF. Understanding these correlates and developing targeted psychosocial interventions may be associated with the improvement of CRF in patients with colorectal cancer.