To investigate the fracture initiation mechanisms and establish the relationship between the ductile fracture mechanism and macro stress–strain for high-strength structural steel, the mechanical response and fracture behavior of Q460C steel and its butt welds were studied via tests, numerical analysis and scanning electron microscopy (SEM) in this paper. The mechanical properties of high-strength steel (HSS) under different stress triaxialities were studied by uniaxial tensile tests on standard specimens and notched round rods. The finite element model is set up according to the characteristic length which is based on SEM observations. By combining experimental results and numerical simulations, the constitutive model and fracture prediction model were established. The relationship between the ductile fracture mechanism and the macro stress strain was obtained. The toughness parameters of the micromechanical model of Q460C steel and its welded joints were compared with those of Q345 steel and seven other types of structural steel from the United States and Japan. The results show that the characteristic length of the crack tip is the key factor affecting the accuracy of predicting fracture toughness under a large stress–strain gradient. The toughness predicted by the model is in good agreement with the traditional fracture toughness test results when taking the average value. The experimental results and finite element analysis verified the effectiveness of the VGM and SMCS micromechanical models in predicting the fracture toughness of Q460C steel and its welded joints, which can provide a theoretical basis and practical guidance for the anti-fracture design and application of HSS structures.