This paper describes a research program involving wood-sheathed and cold-formed steel (CFS) framed diaphragm assemblies.The diaphragm’s response to in-plane monotonic and reversed cyclic lateral loading is investigated in an effort to characterize the seismic performance of this assembly. The work presented herein focuses on the response to loading of the isolated diaphragm subsystem and serves as a complementary study to a research project involving the dynamic testing of full-scale two-story CFS framed buildings, known as the CFS–Network for Earthquake Engineering Simulation (NEES) project. Laboratory testing included eight 3.66 × 6.1-m diaphragm specimens, that is, four configurations, comprising oriented strand board (OSB) sheathing screw connected to CFS C-Channel joists. The response to loading is directly related to screw pattern and size, the use of panel edge blocking, and the type of sheathing. By means of a comparison of design and experimental shear strength and stiffness values, the provisions of the AISI S400 standard were shown to be in need of improvement regarding the number of listed diaphragm configurations. Deflection predications at the design load level were considered to be reasonable.