Considering the harm that residual stress causes to the mechanical properties of a weld joint, the evolution mechanisms of transient strain and residual stress distribution are investigated in laser welding of Al 6061, considering that these originate from non-uniform temperature distribution and are intensified further by the unbalanced procedure of melting and solidification. Thermal-elastic-plastic finite element method is developed and analyzed, while the actual weld profile is novel fitted by a B-spline curve. Transient strain is extracted by strain gauges. Longitudinal strain starts from a fluctuating compressive state and progresses to an ultimate residual tension state at the starting and ending welding positions, respectively. The maximum fitting deviation of the weld profile is 0.13 mm. Experimental and simulation results of residual strain are 842.0 μ and 826.8 μ, with a relative error of 1.805% at the starting position and −17.986% at the ending position. Near the weld center, mechanical behavior is complexly influenced by thermal expansion and contraction in the weld zone and the reaction binding force of the solid metal. Within a distance between −10 mm and 10 mm, and longitudinal stress is in a tension state, transverse stress fluctuates with a high gradient (~100 MPa).