The effect of different heat inputs of 1.45 kJ/mm, 1.78 kJ/mm and 2.31 kJ/mm on the microstructure and mechanical properties of deposited metals of the self-developed AWS A5.28 E120C-K4 high strength steel flux-cored wire was studied by optical microscope, scanning electron microscope and mechanical property test. With the increase in heat input, the results showed that the microstructure of deposited metals became coarse. Acicular ferrite increased at first and then decreased, granular bainite increased and degenerated upper bainite and martensite decreased slightly. Under the low heat input of 1.45 kJ/mm, the cooling rate was fast and the element diffusion was uneven, which caused composition segregation and easy to form large size inclusions SiO2-TiC-CeAlO3 with weak binding to the matrix. Under the middle heat input of 1.78 kJ/mm, the composite rare earth inclusions in dimples were mainly TiC-CeAlO3. The dimples were small and uniformly distributed, and the dimple fracture mainly depended on the wall-breaking connection between medium-sized dimples rather than an intermediate media. Under the high heat input of 2.31 kJ/mm, SiO2 was easy to adhere to high melting point Al2O3 oxides to form irregular composite inclusions. Such irregular inclusions do not need to absorb too much energy to form necking. Finally, the integrated effects of microstructure and inclusions resulted in the optimum mechanical properties of deposited metals with a heat input of 1.78 kJ/mm, which was a tensile strength of 793 MPa and an average impact toughness at −40 °C of 56 J.