Extracellular vesicles (EVs) including exosomes act as intercellular communicators by transferring protein and microRNA cargoes, yet the role of EV lipids remains unclear. Here, we show that the pro-tumorigenic action of lymphoma-derived EVs is augmented via secreted phospholipase A2 (sPLA2)-driven lipid metabolism. Hydrolysis of EV phospholipids by group X sPLA2, which was induced in macrophages of Epstein-Barr virus (EBV) lymphoma, increased the production of fatty acids, lysophospholipids, and their metabolites. sPLA2-treated EVs were smaller and self-aggregated, showed better uptake, and increased cytokine expression and lipid mediator signaling in tumor-associated macrophages. Pharmacological inhibition of endogenous sPLA2 suppressed lymphoma growth in EBV-infected humanized mice, while treatment with sPLA2-modified EVs reversed this phenotype. Furthermore, sPLA2 expression in human large B cell lymphomas inversely correlated with patient survival. Overall, the sPLA2-mediated EV modification promotes tumor development, highlighting a non-canonical mechanistic action of EVs as an extracellular hydrolytic platform of sPLA2. Display omitted •sPLA2-X is induced in EBV-induced B cell lymphoma in humanized mice•sPLA2-X hydrolyzes EV membranes to increase lipid mediator cargo•sPLA2-X alters the morphology and function of EVs•sPLA2-X facilitates EBV lymphomagenesis via a lipid-driven non-canonical mechanism EVs act as intercellular communicators by transferring miRNAs and proteins. Kudo et al. find the importance of EV lipids in EBV lymphoma development. Hydrolysis of phospholipids in tumor-cell-derived EVs by sPLA2-X increases vesicle aggregation, produces immunoregulatory lipid mediators, and facilitates EV uptake by recipient macrophages, thereby exacerbating lymphomagenesis.