In this article, a high data rate and energy-efficient multiple-input multiple-output transmission scheme is considered by combining two popular and rational modulation techniques: spatial modulation (SM) and code index modulation-spread spectrum (CIM-SS). Since in the considered system, called generalized CIM-SM (GCIM-SM), incoming information bits determine modulated symbols, activated transmit antenna indices as well as their corresponding spreading code indices, data bits are conveyed not only by modulated symbols but also by the indices of the active antenna and spreading codes. Hence, a GCIM-SM scheme accommodates faster data rates while spending less transmission power and possessing better error performance compared to the conventional direct sequence spread spectrum (DS-SS), SM, quadrature SM (QSM), and CIM-SS systems. The mathematical expressions of the GCIM-SM system for bit error rate, throughput, energy efficiency, and the system complexity are derived to analyze the overall system performance. Besides, it has been shown via computer simulations that the GCIM-SM system has lower transmission energy, faster data transmission rate, and better error performance than DS-SS, SM, QSM, and CIM-SS systems. Performance analysis of the considered system was performed on Rayleigh block-fading channels for quadrature amplitude modulation technique.