Tungsten (W) is the most promising material for future plasma-facing materials. Its alloys or composites reinforced with various compounds have been studied to improve the irradiation resistance of W. This study aimed to investigate the effect of boron-containing reinforcement in the W matrix against He+ ion irradiation. Cerium hexaboride (CeB6) particulates, which have high neutron shielding properties, were incorporated into the W matrix pre-alloyed by 1 wt% Ni (W1Ni). CeB6 powders were home-made and prepared from CeO2/Mg/B2O3 powder blends via mechanochemical synthesis and purification steps. 1, 5, and 10 wt% CeB6 powders were added to pre-alloyed W1Ni by mechanical alloying, and then they were consolidated by using pressureless sintering (PS, 1400 °C, 1 h) and spark plasma sintering (SPS, 1410 °C, 1 min) techniques. CeB6 particle-reinforced W1Ni composites contained different amounts of reinforcements were prepared by two different sintering methods and were compared with respect to their compositional, microstructural, and microhardness properties and wear and irradiation behaviors. Based on the results, increasing the CeB6 reinforcement amount in the composite triggered the formation of the W2B phase, especially in the W1Ni–10CeB6 composite after both sintering methods. The mechanical and irradiation properties were enhanced more by increasing the CeB6 amount in the case of using the SPS method. When compared to other sintered samples, the SPS'ed W1Ni–10CeB6 composite has the lowest specific wear rate of ∼4 × 10−7 mm3/Nm and the maximum hardness value of ∼21 GPa. According to surface deformation, the W1Ni–5CeB6 composite exhibited comparatively higher resistance to He+ ion irradiation.