While investigating a giraffe death in a Vietnamese zoo, we successfully identified and isolated lumpy skin disease virus (LSDV) from skin nodule biopsies and ruptured nodule wound swab samples. Phylogenetic analysis indicated that the isolate obtained in this study was closely related to the previous Vietnamese and Chinese LSDV strains from cattle. This is the first report on the genome detection and isolation of LSDV in a diseased giraffe in Vietnam. Further study is needed to better understand the epidemiology of this disease in wildlife.