Tenon-mortise joint is widely used in traditional timber structures around the world. This paper summarizes the results of an experimental study of the structural behavior of tenon-mortise joints made with glulam and CNC technology instead of traditional material and manual work. 30 full-scale tenon-mortise joints were manufactured and tested under monotonic loading, and the effects of dimension, shape, processing error and adhesive were evaluated. It was found that the round rectangular shaped tenon-mortise joints were comparable with traditional joints in terms of structural performance, but were time and labor saving. The variability of the proposed tenon-mortise joints was lower, which would benefit the design value. Applying adhesive between tenon and mortise increased the average stiffness by 4.3 times and average moment capacity by 27.4%, respectively. The gaps between wood members had little effect on the capacity and stiffness in monotonic bending but may influence the energy dissipation ability in cyclic bending. This study showed the feasibility of combining the traditional joinery method with modern wood products and manufacturing technology, which may promote the application of tenon-mortise joints in modern timber structures.