Background: Leprosy continues to be a public health focus in endemic countries, with encouraging progress and ongoing opportunities for improved elimination strategies. This study provides an in-depth assessment of clinico-epidemiological trends and outcomes observed from 2020–2024 at a tertiary care center, offering valuable insights into post-pandemic disease patterns and solution-oriented approaches. Methods: This retrospective review encompassed all new leprosy cases over five years, utilizing advanced statistical methodologies including time series analysis, trend assessment, and regression modelling. Demographic, clinical, reactional, disability, and rehabilitation data were carefully collected and analysed using descriptive statistics, comparative analyses, and longitudinal trend evaluations. Results: Five hundred twenty-three new leprosy cases were identified (2020–2024) with discernible temporal variation. Multibacillary (MB) presentations predominated (95.6%, n=500), demonstrating the importance of ongoing early detection initiatives. Males accounted for 57.5% of cases, yet a narrowing gender gap was observed, reflecting positive developments in healthcare access. Grade 2 disability (G2D) rates averaged 17.0%, peaking at 19.7% in 2023, suggesting opportunities for further enhancement of preventive efforts. Leprosy reactions increased over six-fold in the period, highlighting the need for vigilant management strategies. Paediatric cases formed 5.9% of the cohort, with a 29.0% disability rate, pointing to areas for focused intervention. Conclusions: Commendable advances in leprosy control and management are evident. Continued progress will benefit from intensified early case detection, expanded disability prevention, and robust reaction management—cornerstones for achieving national and global elimination goals.