Cylinders made of tantalum (Ta) and tubes made of 304 stainless steel (304SS) were successfully joined by laser welding under different offsets. The experimental results indicated that satisfactory weld formations were obtained. The fusion zone (FZ) was found to consist of the Fe-Cr solution and the Fe2Ta phase. In addition, the intermetallic compounds (IMCs) layer was generated at Ta/FZ interface. When the laser beam offset was -0.2 mm (0.2 mm laser beam offset on the 304 stainless steel side), the interfacial IMC consisted of Fe2Ta. Thicker IMC with the compositions of Fe2Ta+FeTa was generated at offsets of 0 mm (center) and +0.2 mm (0.2 mm laser beam offset on the Ta side). Numerical simulation results showed that the interfacial peak temperature would be increased when the laser beam offset from 304 stainless steel side to Ta side, which led to the thicker IMC and new generation of FeTa. The microhardness in the FZ also fluctuated since the FZ was composed of hard Fe2Ta and soft Fe-Cr solution. Tensile test results indicated that the highest value of 308.3 MPa was obtained under the laser beam offset of -0.2 mm.