Metal additive manufacturing (AM) is gaining broad interest and increasing use in the industrial and academic fields. However, the quantification and commercialization of standard parts usually require extensive experiments and expensive post-characterization, which impedes the rapid development and adaptation of metal AM technologies. In this work, a similarity-based acceleration (S-acceleration) method for design of experiments is developed using K-means clustering and Gaussian Mixture Model (GMM) unsupervised learning algorithms to reduce the time and costs associated with unveiling process-property (porosity defects) relationships during manufacturing. With S-acceleration, part semantic features from machine-setting parameters and physics-effects informed characteristics are explored for measuring mutual part similarities. A user-defined simplification rate of experiments is proposed to purposely remove redundant parts before conducting experiments printing without sacrificing information gain as original full factorial experiment design. This S-acceleration design of experiments is demonstrated on a Concept Laser M2 Dual-laser Cusing machine for the experimental plan of modeling relationships between process parameters and part porosity defects. The printed part has 2 mm diameter × 4 mm tall pin geometry considering variations in build location and orientation, laser settings and powder feedstock are held constant. In total, 242 parts are measured to create a “ground truth” data set of porosity levels by using X-ray tomography microscopy. The S-acceleration method is assessed for performance considering 40%, 50%, and 60% of user-defined experiment simplification rates. The repeated experiments are removed without ignoring the minority experiments outlier, assuring a similar process-property relation in the original experiment plan. The experiment number is significantly reduced based on part similarity with minimal compromise of model accuracy and obtained knowledge.