Polyamide thin-film composite (PA-TFC) membranes make large-scale desalination effective. Interfacial polymerization (IP) is used to make PA-TFC membranes, but it may limit the range of monomers that can be used, which hinders progress toward advanced membranes. Layer-by-layer (LbL) sequential deposition could circumvent kinetic and thermodynamic limitations of the conventional IP process to facilitate incorporation of different co-monomers into the membrane. The selective layer needs to be deposited onto a microporous support, but depositing LbL coatings on microporous supports often results in defective membranes. Using a poly(vinyl alcohol) (PVA) primer between the support and the LbL polyamide layer may prevent defect formation. The water permeance and salt rejection of a three layer, PVA-primed, LbL-based PA-TFC membrane are discussed and compared to a membrane made without the PVA primer and a commercially available membrane. Mass transfer resistances are analyzed using a series resistance model and appear to be small or even negligible compared to that of the polyamide layer. Incorporation of a sulfonated co-monomer into the polyamide via LbL is reported. The combination of a PVA primer layer and LbL sequential deposition may expand the range of co-monomers that could be used relative to polyamide membranes prepared by the conventional IP process.