Background: Modern therapeutics and health care improvements prolong stroke patients’ survival; however, the degree of disability remains high. Stroke survivors often require caregivers, particularly in the first year after the onset of the stroke. Longitudinal assessment of and factors associated with caregiver burden (CGB) among caregivers of stroke patients has been scarcely discussed. This study aimed to define the changes in CGB in the first year of caregiving among the caregivers of stroke patients and to identify associated factors. Methods: A prospective, multi-centered observational study was conducted in nine public hospitals in Mongolia. We used the Montgomery CGB Scale for assessing CGB, and repeated the assessment after 1 year. Stroke patient characteristics were included in the analyses. Multinomial logistic regressions were conducted to analyze changes in CGB. Results: A paired t-test analysis revealed that demand burden increased (from 12.61 to 11.50, p = 0.034), whereas stress burden decreased (from 10.69 to 11.60, p = 0.016). Although objective burden decreased, the difference was not significant. Factors associated with these changes in CGB were the caregiver’s marital status, the caregiver’s relationship with the patient, financial difficulties, and the patient’s sex and dependency. Discussion: The information on factors predicting changes in CGB in the first year of caregiving provided in this study suggests that social or financial support can assist in reducing CGB among the caregivers of post-stroke patients.