Background This study reviews the progress of leprosy elimination in Yunnan, China, over the past 30 years and identifies the challenges for the next stage of the program. Methodology/Principal findings Data were collected from the Leprosy Management Information System in China (LEPMIS). The progress made in the elimination of leprosy between 1990 and 2019 was measured. We defined two time periods, time period 1 (1990-2003) and time period 2 (2004-2019), because multidrug therapy (MDT) was launched for the treatment of leprosy in 1990 and a special fund from the central government was established for leprosy in 2004. During the past 30 years, the number of newly detected leprosy patients in Yunnan has steadily declined. In total, 703 newly detected leprosy patients were reported in 1990, and 353 and 136 cases were reported at the end of 2003 and 2019, respectively. At the end of 1990, 90.7% (117/129) of counties in Yunnan Province were identified as leprosy-endemic counties (>1 case per 100,000 population). By the end of 2003 and 2019, 39.3% (46/117) and 85.5% (100/117) of the leprosy-endemic counties, respectively, had dropped below the elimination threshold. The main challenges are the remaining leprosy-endemic counties, the high rate of cases with a contact history, insufficient early detection, and leprosy cases resulting in physical disability. Conclusions/Significance A multifaceted strategy for leprosy elimination in Yunnan Province has been successfully implemented, and remarkable progress has been made in the elimination of leprosy in this area. The priorities for leprosy elimination in the next stage are securing sustainable support and investment from the government, establishing an effective surveillance system, ensuring prompt early detection, providing treatment with MDT, preventing transmission of M. leprae, preventing disability, providing health education, and preventing recurrence of the epidemic situation of leprosy. Author summary Compared to other provinces in China, Yunnan bears a significant burden of leprosy disease. Multidrug therapy (MDT) was launched for leprosy in 1990, and a special fund for leprosy was established in Yunnan Province by the central government in 2004. During the past 30 years, the number of newly detected leprosy patients has steadily declined, accompanied by an enormous decrease in the number of leprosy-endemic regions. Compared to the 1990-2003 period, the period after the establishment of the special fund from the central government (2004-2019) saw a decrease in the proportion of child cases and patients with grade 2 disability (G2D) and in the duration of delay in diagnosis among newly detected patients, while the proportion of patients with paucibacillary (PB) leprosy, the proportion belonging to minority groups, and the proportion of cases detected early increased significantly. The main challenges are the remaining leprosy-endemic counties, the high rate of cases with a contact history, insufficient early detection, and cases resulting in G2D. To eliminate leprosy in Yunnan Province, a multifaceted strategy should be implemented.