This study aimed to characterize the complete genome of an Egyptian strain of Zucchini Yellow Mosaic Virus (ZYMV), identify key genetic elements linked to aphid transmission, and analyze its phylogenetic relationship with global ZYMV strains. A single necrotic local lesion technique was used for the biological purification of a Zucchini yellow mosaic virus (ZYMV) strain from the Eskandarani squash cultivar, and the purification was confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR). Flexuous filament virions with a size of 11 × 730 nm were purified. The complete nucleotide sequence of the ZYMV genome, consisting of 9591 nucleotides, was obtained and deposited in GenBank (accession numbers: LC795783.1 for nucleotides and BFD45315.1 for protein). The genome encodes a polyprotein of 3080 amino acids (~350 kDa). The genome of the Egy-1920 strain contains ten genes, mainly P1, HC, P3, 6K1, C1, 6K2, NIa-VPg, NIa-Pro, NIb, and cp, with sizes ranging from 156 to 1902 nucleotides. The strain exhibited high nucleotide (92.58–99.93 %) and protein (95.68–99.81 %) sequence identity compared to 45 global ZYMV strains, showing significant homology to Taiwanese and Chinese strains. Phylogenetic analysis placed the Egy-1920 strain in close relation to Taiwanese ZYMV strains. Bioinformatics analysis of the helper component (HC) protein revealed three aphid-transmission motifs. The genome length variation (9243-9947 nts) among ZYMV strains was also discussed. The results pave the way for the development of reliable diagnostic techniques and the detection of possible therapy targets for ZYMV control. The findings of this study will contribute to the development of enhanced diagnostic methods and potential therapeutic strategies for effective ZYMV control.