The influences of laser welding velocity, flow rate of side-blow shielding gas, defocusing distance and other parameters on the full penetration laser weld seam of K418 and 42CrMo were experimentally investigated using continuous wave Nd∶YAG laser. Results show that the asymmetric cross-sections of weld seams exhibit X shape or T shape. With increasing welding velocity, the linear heat input and dimension of weld seam decrease, and the shape of it changes from X shape to T shape. Meanwhile, the rate of change in dimension of weld bottom region is larger than that of weld top region. The change of the top surface width of the weld seam is small under the condition that defocusing distance changes within the range of Rayleigh length; the top surface widths of the weld seam increase quickly under the condition that defocusing distance changes out of the range of Rayleigh length with enough density of laser power. The high-quality of weld seam with constant 3 kW laser power and 35° angle of side-blow shielding gas can be obtained by optimizing welding velocity, flow rate of shielding gas, defocusing distance and other parameters.