An epidemiological study spanning twelve years has revealed that sheeppox disease is both widespread and endemic, predominantly surging during the winter and summer seasons. This investigation focused on sheeppox across 11 field outbreaks, involving 889 animals from non-migratory flocks across six districts in Karnataka, in the southern peninsula of India. Among these, 105 animals exhibited clinical signs suggestive of sheeppox, such as lesions on the body, and 95 cases were confirmed through PCR testing. The overall positivity rate for sheeppox stood at 10.68% (95 out of 889 animals). The incidence of sheeppox was notably higher in animals aged between 1 and 2 years and was more prevalent in females. Affected animals displayed symptoms including respiratory distress, weakness, fever, loss of appetite, depression, and various skin lesions ranging from papular to pock lesions across their bodies. There was a significant increase in total leukocyte count, while hemoglobin levels, red blood cell counts, and hematocrit values significantly decreased. On gross examination, sheeppox lesions, varying from vesicular to nodular forms, were predominantly found on hairless areas of the body. Microscopic examination of skin lesions revealed extensive changes, such as hyperkeratosis, parakeratosis, acanthosis, hydropic degeneration, and necrosis of epithelial cells, along with characteristic intracytoplasmic viral inclusions. The lungs exhibited type-II pneumocyte hyperplasia and proliferative bronchiolitis, also with intracytoplasmic inclusions. Confirmation of the sheeppox virus was achieved through PCR and subsequent sequence analysis. Phylogenetic analysis of the full-length P32 and RPO30 gene demonstrated homology with sheeppox isolates from various parts of India and neighboring countries, indicating that Indian sheeppox viruses are highly lineage-specific and correlate with the host of origin. Based on these findings, it is recommended to implement a homologous vaccination strategy, utilizing selective host/viral strains to enhance protection in susceptible animals.