Surface and internal defects formed upon laser beam welding (LBW) have been recognized as a serious problem because they cause stress concentration leading to premature failure of a welded component. This paper seeks to remedy these weld imperfections by applying various post-weld treatments and analyzing their effect on the high cycle fatigue (HCF) performance of welded joints. High efficiency of laser-based post-processing techniques after welding such as laser surface remelting (LSR) and laser shock peening (LSP) was demonstrated and compared with conventional approaches. The study reveals that welding porosity determines the internal crack initiation of the surface-treated weldments. Influence of process parameters on porosity level and the HCF properties is presented in detail. Based on an extensive experimental study, practical guidelines needed to mitigate the notch effect from defects and to maximize the fatigue performance of the laser-welded Ti-6Al-4V butt joints are given.