A polyamide (PA) thin film composite (TFC) reverse osmosis (RO) membrane having high permselectivity and excellent mechanical/chemical durability was prepared using a polyethylene (PE) support. Although the PE support's uniform pores and high surface porosity are beneficial for enhancing membrane permselectivity, its intrinsic hydrophobicity makes the fabrication of a PA selective layer challenging. An oxygen plasma treatment on the PE support, combined with using a sodium dodecyl sulfate (SDS) during interfacial polymerization, allowed a PA layer to be formed on the support due to by enhancing its water wettability. The systematic optimization of the membrane fabrication parameters (e.g., plasma pretreatment, monomer and SDS compositions and post-heat treatment) achieved high membrane performance. The fabricated PE-supported membrane (TFC-PE) showed similar to 30% higher water flux with similar to 0.4% enhancement in NaCl rejection compared to a commercial RO membrane. Furthermore, the TFC-PE membrane had mechanical properties and organic solvent resistance superior to the commercial membrane, which is attributed to the excellent mechanical and chemical stability of the PE material. The proposed strategy could expand the application of RO membranes to mechanically and chemically harsh operating environments.