In this article, the influence of simulated thermal cycles for the heat-affected zone (HAZ) on the microstructural evolution and mechanical properties in a low-carbon high-strength Cu-bearing steel was investigated by microstructural characterization and mechanical tests. The results showed that the microstructure of the coarse-grained heat-affected zone (CGHAZ) and the fine-grained heat-affected zone (FGHAZ) was mainly comprised of lath martensite, and a mixed microstructure consisting of intercritical ferrite, tempered martensite and retained austenite occurred in the intercritically heat-affected zone (ICHAZ) and the subcritically heat-affected zone (SCHAZ). Also, 8–11% retained austenite and more or less Cu precipitates were observed in the simulated HAZs except for CGHAZ. Charpy impact test indicated that the optimum toughness was obtained in FGHAZ, which was not only associated with grain refinement, but also correlated with deformation-induced transformation of the retained austenite, variant configuration as interleaved type and a relatively weak variant selection. The toughness of ICHAZ and SCHAZ exhibited a slight downtrend due to the presence of Cu precipitates. The CGHAZ has the lowest toughness in the simulated HAZs, which was attributed to grain coarsening and heavy variant selection. In addition, the contribution of Cu precipitates to yield strength in simulated HAZs was estimated based on Russell–Brown model. It demonstrated an inverse variation trend to toughness.