A 4 kW fiber laser was chosen to weld the new hot-rolled nano-scale precipitation-strengthened steel with a thickness of 4.5 mm. The effect of laser power, defocusing distance, and welding speed on the welded joint appearance was examined, and the microstructure and mechanical properties on the typical butt joints were investigated. Results showed that increasing laser welding power may cause faster downward flow of molten metal to produce greater root humping. With the welding speed increasing, the average welding seam (WS) width decreased, and the average WS and heat-affected zone (HAZ) hardness increased. The microstructures of WS, fusion line, and coarse grain heat-affected zone were lath martensite, but the growth direction of the original austenite grain boundaries was significantly different. The microstructures of fine grain heat-affected zone were ferrite and martensite, and the microstructure of mixed grain heat-affected zone contained ferrite, massive M/A island, and a small amount of martensite. The micro-hardness values of WS, HAZ, and base metal (BM) were 358, 302, and 265 HV, respectively. The butt joint fracture at the BM far from the WS and the welded joint tensile strength are observed to follow proportional relationship with hardness.