The density profile, mechanical properties, strength potential index, and microstructure changes of hybrid poplar were investigated before and after high-pressure (HP) treatments. The results of density profile indicated that a high uniform density distribution was developed inside the pressurized wood samples. The mechanical properties results showed that the HP treatments significantly increased (P < 0.05) the modulus of elasticity (MOE), the modulus of rupture (MOR), and the Brinell hardness (BH) of the densified wood at selected conditions. Of all the wood samples, the compressed wood at 150 MPa condition possessed the highest density and strength properties. Considering the variation in strength properties along with density, it can be concluded that the compression destruction degree of HP treatment was comparable with that caused by optimized thermal compression technique based on the strength potential index results. The integrity of wood cells presented in scanning electron microscopy results demonstrated the compression of wood cell wall achieved by HP treatment without causing any fractures, which further indicated that HP treatment is a less destructive compression technology. Based on this research, HP treatment has great potential to be applied in wood densification for commercial use.