Several 0.4C-Cr-Mo-Ni steels with different sulfur and calcium levels have been studied to determine the effect of the morphology of nonmetallic inclusions on the mechanical properties of quenched and tempered low-alloy structural steels. Stringy MnS inclusions appearing in the steel containing sulfur at a commercial level produced a remarkable anisotropy in the fracture ductility (ε f ) for tempers of 473 and 923 K. The fine elliptical MnS inclusions that precipitated in the desulfurized steels at low sulfur levels of 0.002 mass% had a detrimental effect on the ε f for the temper of 473 K but a beneficial effect on the ε f for the temper of 923 K. Fine particle inclusions that appeared in the calcium-treated steel coupled with a low sulfur content of 0.002 mass% were quite effective in improving the isotropy regarding the fracture ductility for tempers of 473 and 923 K. However, two cluster types of composite inclusions associated with the calcium-treated steel containing sulfur at a commercial level produced a detrimental effect on the isotropy regarding the ε f independent of the tempering conditions. The results are described and discussed.