Cr5Mo steel with high thermal strength is frequently applied as the material for hydrocracking furnace tubes. Nonetheless, Cr5Mo tubes are prone to material failure in a high-temperature environment, threatening production safety. Considering that the IN718 nickel-base superalloy has favorable high-temperature oxidation resistance, the IN718 coating was fabricated on Cr5Mo substrate through laser cladding. The effect of process parameters on the high-temperature oxidation resistance of laser cladding IN718 coating was investigated. The results confirm that laser power and scanning speed affected the eutectic quantity precipitation of this layer, and the eutectic quantity precipitation was positively correlated with the mass gain of the coating. The high-temperature behavior of the coating could be divided into surface oxidation, intergranular corrosion, and material shedding. The scanning speed has a more significant impact on the high-temperature oxidation resistance. When the scanning speed is 15 mm/s, cracks originating in the heat-affected zone could exert a negative impact on the high-temperature oxidation resistance.