Pre-loading on engineering materials or structures may produce pre-strain, especially plastic strain, which would change the fatigue failure mechanism during their service time. In this paper, an energy-based method for fatigue life prediction on high-strength-steel welded joints under different pre-strain levels was presented. Tensile pre-strain at three pre-strain levels of 0.2%, 0.35% and 0.5% was performed on the specimens of the material Q345, and the cyclic stress and strain responses with pre-loading were compared with those without pre-loading at the same strain level. The experimental work showed that the plastic strain energy density of pre-strained welded joints was enlarged, while the elastic strain energy density of pre-strained welded joints was reduced. Then, based on the strain energy density method, a fatigue life estimation model of the high-strength-steel welded joints in consideration of pre-straining was proposed. The predicted results agreed well with the test data. Finally, the validity of the developed model was verified by the experimental data from TWIP steel Fe-18 Mn and complex-phase steel CP800.