The objective of this study was to determine significant factors affecting spacio-temporal distribution of lumpy skin disease (LSD) in Mashonaland West Province of Zimbabwe. A retrospective study of LSD from year 2000 to 2013 was undertaken using records from the Department of Livestock and Veterinary Services, Mashonaland West Province, Zimbabwe. Descriptive statistics was computed on LSD cases, treatments, vaccinations, and deaths. Analysis of variance (ANOVA) was used to determine significant factors affecting LSD distribution across diverse farming sectors (localities), districts, months, and years as from 2000 to 2013 in Mashonaland West Province. Districts bordering frequently vaccinated (foot and mouth) and game areas had significantly higher LSD outbreaks (p < 0.05) than those further away. LSD cases were significantly higher (p < 0.05) in resettlement (7.79 ± 1.42) and communal (7.59 ± 1.67) areas where there is sufficient veterinary institutional support than in commercial (6.79 ± 620) and A2 (6.85 ± 1.66) areas, whereas LSD cases were significantly lower (p < 0.05) probably due to under reporting in A1 (3.34 ± 0.46) and small scale (3.60 ± 0.46). Hot wet season had higher (p < 0.05) LSD cases than dry months as highest LSD cases were recorded in March (13.11 ± 5.89). Above normal annual rainfall had significantly higher (p < 0.05) LSD cases than normal and below normal rainfall. The study recommends strengthening of existing veterinary service structures for livestock movement and disease surveillance and vaccination to reduce further spread of the disease.