As the only renewable resource among the four basic materials (steel, cement, plastic, wood), wood itself and wood products have a “low carbon” value and play an important role in storing carbon. The moisture absorption and expansion properties of wood limit its application scope and shorten its service life. To enhance the mechanical and physical properties of fast-growing poplars, an eco-friendly modification procedure has been used. This was accomplished by the in situ modification of wood cell walls by vacuum pressure impregnation with a reaction of water-soluble 2-hydroxyethyl methacrylate (HEMA) and N,N’-methylenebis(acrylamide) (MBA). The anti-swelling efficiency of HEMA/MBA-treated wood was improved (up to 61.13%), whereas HEMA/MBA-treated wood presented a lower weight-gain rate (WG) and water-absorption rate (WAR). It was observed that the modulus of elasticity, hardness, density, and other properties of modified wood had improved significantly, as indicated by XRD analysis. Modifiers diffuse primarily within cell walls and cell interstices of wood, causing crosslinks between the modifiers and the cell walls, reducing its hydroxyl content and blocking the channels for water movement, thereby enhancing its physical properties. This result can be obtained by scanning electron microscopy (SEM) and energy dispersive x-ray spectroscopy (EDX), Nitrogen adsorption test imaging ATR-FTIR (Attenuated total reflection-Fourier-Transform Infrared) Spectroscopy, and nuclear magnetic resonance (NMR) and Nitrogen adsorption test. Overall, this straightforward, high-performance modification method is crucial for maximizing wood’s efficiency and the sustainable development of human society.