Polyamide thin-film composite membranes are critically important in combating global water scarcity. However, simultaneously achieving ultrafast water permeation and high solute rejection remains challenging due to their thick, dense separation layers. Herein, we demonstrate a simple yet versatile strategy to modulate the nanostructure of the polyamide separation layer, particularly the abundance and interconnectivity of free volume, by adopting well-designed aqueous monomers. The key is introducing methyl groups onto the conventional piperazine monomers, which accelerates trans-interfacial diffusion and decreases the ensuing amidation reaction rate. This leads to the formation of a thinner separation layer composed of more linear polyamide fragments, where the methyl groups, serving as "molecular pillar" sites, weaken the intra- and interchain interactions to prevent their dense stacking, thereby creating a more interconnected free volume network. One prepared membrane exhibits a very high water permeance of 57.8 ± 2.8 L m h bar along with a satisfactory per- and polyfluoroalkyl substance rejection over 90%, as well as superior resistance to compression. This molecular-level microstructural engineering provides a new route and fundamental insights into the scalable production of high-performance separation membranes for emerging contaminant removal.