Herein, we report that vascular endothelial growth factor A (VEGF‐A) engages the PI3K/Akt pathway by a previously unknown mechanism that involves three tyrosine kinases. Upon VEGF‐A‐dependent activation of VEGF receptor‐2 (VEGFR‐2), and subsequent TSAd‐mediated activation of Src family kinases (SFKs), SFKs engage the receptor tyrosine kinase Axl via its juxtamembrane domain to trigger ligand‐independent autophosphorylation at a pair of YXXM motifs that promotes association with PI3K and activation of Akt. Other VEGF‐A‐mediated signalling pathways are independent of Axl. Interfering with Axl expression or function impairs VEGF‐A‐ but not bFGF‐dependent migration of endothelial cells. Similarly, Axl null mice respond poorly to VEGF‐A‐induced vascular permeability or angiogenesis, whereas other agonists induce a normal response. These results elucidate the mechanism by which VEGF‐A activates PI3K/Akt, and identify previously unappreciated potential therapeutic targets of VEGF‐A‐driven processes.