The use of aerial platforms such as unmanned aerial vehicles (UAVs), popularly known as drones, has emerged as a promising solution for providing reliable and cost-effective wireless communications. In particular, UAVs can be quickly and efficiently deployed to support cellular networks and enhance their quality-of-service (QoS) by establishing line-of-sight communication links. With their inherent attributes such as mobility, flexibility, and adaptive altitude, UAVs admit several key potential applications in wireless systems. Remarkably, despite these inherent advantages of UAVbased communications, little work has analyzed the performance tradeoffs associated with using UAVs as aerial wireless platforms. The key goal of this dissertation is to develop the analytical foundations for deployment, performance analysis, and optimization of UAV-enabled wireless networks. This dissertation makes a number of fundamental contributions to various areas of UAV communications that include: 1) Efficient deployment of UAVs, 2) Performance evaluation and optimization, and 3) Design of new flying, three-dimensional (3D) wireless systems. For deployment, using tools from optimization theory, holistic frameworks are developed for the optimal 3D placement of UAV base stations in uplink and downlink scenarios. The results show that the proposed deployment approaches significantly improve the downlink coverage for ground users, and enable ultra-reliable and energy-efficient uplink communications in Internet of Things (IoT) applications. For performance optimization, a novel framework is developed for maximizing the performance of a UAV-based wireless system, in terms of data service, under UAVs’ flight time constraints. To this end, using the mathematical framework of optimal transport theory, the optimal cell associations, that lead to a maximum data service to ground users within the limited UAVs’ hover duration, are analytically derived. The results shed light on the tradeoff between hover time and quality-of-service in UAV-based wireless networks. For performance evaluation, this dissertation provides a comprehensive analysis on the performance of a UAV-based communication system in coexistence with a terrestrial network. In particular, a tractable analytical framework is proposed for analyzing the coverage and rate performance of a network with a UAV base station and deviceto-device (D2D) users. The results reveal the fundamental tradeoffs in such a UAV-D2D network that allow adopting appropriate system design parameters. Then, this dissertation sheds light on the design of three new drone-enabled wireless systems. First, a novel framework for effective use of cache-enabled UAVs in wireless networks is developed. The results demonstrate how the users’ quality of experience substantially improves by exploiting UAVs’ mobility and user-centric information. Second, a new framework is proposed for deploying and operating a drone-based antenna array system that delivers wireless service to ground users within a minimum time. The results show significant enhancement in QoS, spectral and energy efficiency while levering the proposed drone antenna array system. Finally, to effectively incorporate various use cases of drones ranging from aerial users to base stations, the new concept of a fully-fledged 3D cellular network is introduced. For this new type of 3D wireless network, a unified framework for deployment, network planning, and performance optimization is developed that yields a maximum coverage and minimum latency in the network. In a nutshell, the analytical foundations and frameworks presented in this dissertation provide key guidelines for effective design and operation of UAV-based wireless communication systems.