Due to the limitations of the energy density and penetration ability of arc welding technology for long-distance pipelines, the deterioration of the microstructures in the coarse-grained heat-affected zone (HAZ) in welded joints in large-diameter, thick-walled pipeline steel leads to insufficient strength and toughness in these joints, which strongly affect the service reliability and durability of oil and gas pipelines. Therefore, high-energy-beam welding is introduced for pipeline steel welding to reduce pipeline construction costs and improve the efficiency and safety of oil and gas transportation. In the present work, two pieces of X100 pipeline steel plates with thicknesses of 12.8 mm were welded by a high-power robot laser-welding platform. The quantitative correlation between thermal cycling and the microstructure of the welded joint was studied using numerical simulation of the welding temperature field, optical microscopy (OM), and scanning electron microscopy (SEM) with energy-dispersive spectroscopy (EDS). The results show that the heat-source model of a Gaussian-distributed rotating body and the austenitization degree parameters are highly accurate in simulating the welding temperature field and characterizing the austenitization degree. The effects of austenitization are more significant than those of the cooling rate on the final microstructures of the laser-welded joint. The microstructure of the X100 pipeline steel in the HAZ is mainly composed of acicular ferrite (AF), granular bainite (GB), and bainitic ferrite (BF). However, small amounts of lath martensite (LM), upper bainite (UB), and the bulk microstructure are found in the columnar zone of the weld. The aim of this paper is to provide scientific guidance and a reference for the simulation of the temperature field during high-energy-beam laser welding and to study and formulate the laser-welding process for X100 pipeline steel.