Light-frame wood structures are the most common type of construction for residential and low-rise buildings in North America. The 2015 edition of the National Building Code of Canada has increased the height limit for light-frame wood construction from 4 to 6 stories. With the increase in building height, it was noticed that light-frame wood structures may be governed by inter-story drift under wind and seismic loads. To reduce the inter-story drift, a hybrid system, consisting of CLT cores and light-frame structures, is proposed. The efficiency of this hybrid system is dependent on the performance of the connections between the two sub-systems. In this project, self-tapping screws (STSs) were used to connect the CLT core and light-frame wood structures on the floor level. Monotonic and reversed-cyclic tests were carried out on CLT-wood frame connections connected with STSs inserted at 45°, 90°, and mixed angles (45° and 90°). The connection performance was evaluated in terms of strength, stiffness, ultimate displacement, ductility, and energy dissipation capacity. Results show that a joint with STSs inserted at 45° had high stiffness and ductility but low energy dissipation, while connections with STSs installed at 90° had high ductility and energy dissipation but low stiffness. Connections with STSs inserted at mixed angles (45° and 90°) achieved the advantages of both configurations when the STSs were inserted at 45° or 90° individually, i.e., high stiffness, ductility, and energy dissipation. The ductility and energy dissipation were significantly improved compared with connections with STSs only inserted at 45° or 90°. This mixed angle connection can be an ideal design for connecting light-frame wood structures to a CLT core to resist wind and seismic load.