Multidrug-resistant tuberculosis (MDR-TB) is a global public health threat and burden on the health system. This is especially the case in high tuberculosis (TB) prevalence countries, such as Sudan. Consequently, this study aimed to ascertain the predictors of MDR-TB in Sudan to provide future guidance. An unmatched case-control study to assess the predictors of MDR-TB infections among the Sudanese population was conducted from August 2017 to January 2018 at Abu-Anga referral hospital. Patients’ data was gathered from patients’ cards and via interviews. A structured pre-validated questionnaire was used to gather pertinent information, which included sociodemographic characteristics and other relevant clinical data. Univariate and multivariate logistic regression analysis was employed to determine the predictors of MDR-TB infection. 76 of the 183 patients interviewed (41.5%) had MDR-TB cases. The independent predictors for MDR-TB were living in rural areas [adjusted odds ratio (aOR) = 3.1 (95% confidence interval (CI): 1.2–8.2)], treatment failure [aOR = 56.9 (10.2–319.2)], and smoking [(aOR = 4 (1.2–13.2)], whereas other sociodemographic factors did not predict MDR-TB. In conclusion, the study showed that a history of smoking, living in rural areas, and a previous treatment failure were the predictors of MDR-TB in Sudan. The latter factors are most likely due to issues that are related to access and adherence to treatment and lifestyle. The existence of any of these factors among newly diagnosed TB patients should alert clinicians for the screening of MDR-TB. The implementation of directly observed treatment (DOT) and health education are crucial in stopping the spread of MDR-TB in Sudan.