(1) Background: Tuberculosis remains a public health problem in the world. The study analyzed the factors associated with drug-resistant tuberculosis in the prison population of the state of Paraná. (2) Methods: Ecological study of drug-resistant tuberculosis cases registered in the Paraná Information System, Brazil (2008 to 2018). We performed descriptive statistics of quantitative parameters calculated with absolute frequencies. Additionally, we used binary regression logistics, where the odds ratio with its respective confidence interval was calculated. (3) Results: Of the 653 cases registered as cases of tuberculosis in the incarcerated population, 98 were drug-resistant tuberculosis. We observed that educational level of up to 8 to 11 years of schooling, negative bacterial culture (test outcome) and no tobacco use were factors associated with the non-development of drug-resistant tuberculosis, while clinically confirmed pulmonary TB and positive sputum smear microscopy in the fourth month of follow-up showed an association for the development of drug resistance. (4) Conclusions: The study showed that clinically confirmed pulmonary TB and a positive sputum smear microscopy in the fourth month of follow-up were associated with drug-resistant tuberculosis.