Objectives: The aim of this study was to describe the secular trends in drug-resistant tuberculosis (DR-TB) and to identify unique characteristics of multidrug-resistant tuberculosis (MDR-TB) in rural China. Methods: A retrospective study was conducted using TB data collected from 36 TB prevention and control institutions serving rural populations in Shandong Province, China, for the period 2006–2015. Results: Approximately 8.3% of patients suffered from MDR-TB, among whom 70% were newly treated patients; this rate increased by 1.3% annually during the 10-year study period. An increase in the percentage of overall first-line drug resistance against isoniazid, rifampicin, ethambutol, and streptomycin was confirmed (p < 0.05). The percentage of MDR-TB in new and previously treated cases increased at yearly rates of 9.9% and 11.1%, respectively. MDR-TB patients were more likely to be female (odds ratio (OR) 1.58, 95% confidence interval (CI) 1.32–1.89), smokers (OR 1.75, 95% CI 1.47–2.07), to have had recent TB contact (OR 1.58, 95% CI 1.04–2.42), or to have been retreated (OR 2.89, 95% CI 2.46–3.41). Conclusions: Increasing MDR-TB and rates of primary MDR-TB characterize DR-TB cases in rural China. Persistent efforts need to be made among MDR-TB patients in future TB control strategies. Keywords: Multidrug-resistant tuberculosis, Primary transmission, Rural, Epidemiology