The purpose of the current study was to formulate ethosomal transdermal polymeric patch containing losartan potassium for the treatment of hypertension. Ethosomes are the soft, malleable vesicles which in one of the most widely known novel and non-invasive drug delivery system. At the very onset, ethosomes were prepared by varying the concentration of lipids then the prepared ethosomes were incorporated in the prepared Eudragit RS100 and Eudragit RL100 patch. Preformulation studies, FTIR and DSC analysis showed that the drug and excipients do not have any interaction. After that the prepared ethosomal formulation was characterized for the particle size, zeta potential, PDI, Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Atomic Force Microscopy (AFM), % encapsulation efficiency and in-vitro drug release study. The patch was evaluated for the weight variation, thickness, folding endurance, tensile strength, %moisture content, in-vitro release study, in-vivo study, and stability study. The optimized ethosomal formulation EF5 shows a particle size of 112.2 ± 1.3 and zeta potentials of −59 ± 0.8 mV along with the 89.21 ± 2.82 % encapsulation of losartan potassium and 86.45 ± 0.02 release of drug in 72 h from the ethosomes. In-vivo study shows that an optimized patch significantly treats hypertension as compared to the losartan potassium. The transdermal patch shows maximum stability at 4 °C/60 ± 5RH. These results suggest that the transdermal delivery of losartan potassium in the form of ethosomal transdermal polymeric patch can provide a sustained effect in the treatment of hypertension.