A 3D thermal elastic-plastic finite element model to predict welding residual stresses induced by full-penetration laser welding of Ti6Al4V alloy was described in detail. The welding experiments and residual stresses measurements by through-thickness hole-drilling method were also performed to validate the simulated results. A uniform conical heat source model with parameters taken from the actual weld seam dimensions was developed to simulate the welding temperature fields with different welding heat inputs. The thermal elastic-plastic finite element simulation was employed to calculate the welding residual stresses. The boundary conditions and the size of finite element mesh were also discussed. The results show that the cross section profiles of the weld seam simulated with the conical heat source based on the configuration of weld seam agree well with the experimental results; the zone of residual stresses distribution in laser full-penetration welding of Ti6Al4V alloy is very narrow and the gradient of longitudinal residual stress is very steep; the residual stresses distribution on the surfaces are different from those in the interior of the welding seam; the measured residual stresses by through-thickness hole-drilling method are similar to the simulated ones in the interior of the welding seam.