Abstract: This study investigates the microstructure and co-precipitation behavior of multicomponent (Ni(Al,Mn) and Cu) nanoparticles in the weld heat-affected zones of high-strength low-carbon steel. Through thermal simulations, the intercritical, fine-grained, and coarse-grained heat-affected zones were systematically characterized to elucidate the interplay between the microstructure, precipitation, and mechanical properties. At a heat input of 30 kJ·cm⁻¹, Ni(Al,Mn) nanoparticles dissolve in the intercritical heat-affected zone, followed by dense reprecipitation coupled with significant coarsening of Cu particles during cooling, thereby retaining high strength but reducing impact toughness to (142 ± 10) J (compared to (205 ± 8) J of the base metal). The fine-grained heat-affected zone, under the same heat input, exhibits a refined ferritic–bainite matrix with a few fine Ni(Al,Mn) and slightly coarsened Cu particles, thus enhancing plastic deformation capacity and resulting in superior impact toughness of (196 ± 7) J. Despite complete dissolution of original precipitates at peak temperatures in the coarse-grained heat-affected zone, re-precipitated nanoparticles provide effective strengthening effect, compensating for grain coarsening and dislocation recovery and resulting in an impressive impact toughness of (186 ± 6) J. The toughening mechanism is primarily attributed to the synergistic actions of the matrix, precipitates, and deformation twins. These findings provide mechanistic and quantitative insights for developing processing–microstructure–property relationships in different welding heat-affected zones, and this framework can be further utilized to optimize welding parameters for tailored applications.