Tuning the reactivity and diffusion of amine monomers in interfacial polymerization (IP) process could efficiently regulate the formation and structure of the polyamide (PA) selective layer. Herein, novel thin-film composite NF membranes with dense and ultrathin PA selective layer were fabricated using 1,3,5-benzenetricarbonyl trichloride (TMC) and ultra-low concentration triaminoguanidine (Tg) as reactive monomers. Fabrication parameters, including Tg concentration, NaOH concentration and reaction time, were systematically explored to optimize the desalination performance of PA-Tg NF membrane. During the stability test over 48 h, PA-Tg-0.06 membrane displayed a water permeance of ∼12 L m−2 h−1·bar−1 and Na2SO4 rejection of ∼99%. Meanwhile, detailed comparisons were made between PA-Tg NF membrane and a typical NF membrane fabricated with PIP as an aqueous monomer, including characteristics of the monomers as well as the structure, water permeance, salt rejection and antifouling property of the membranes. Molecular dynamics simulation and interfacial diffusion experiments indicated that the Tg monomer exhibited a higher reactivity but a lower diffusivity than the PIP monomer, making it feasible for the fabrication of PA-Tg NF membrane with ultra-low concentration of Tg monomer. In addition, compared with the PA-PIP membrane, the PA-Tg membrane exhibited a smoother, more hydrophilic and negatively charged surface, as well as a thinner and denser selective layer, thereby showing a higher water permeance, salt rejection and stronger fouling resistance.