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This dissertation investigates the creation and diffusion of technological novelty, a key driver of innovation, technological change, and economic development. The thesis is structured around three interconnected empirical chapters. Chapter 2 explores two of the most prominent approaches in the innovation literature for measuring technological novelty and examines whether these indicators capture complementary or distinct aspects of novelty as well as their respective power in predicting the value of inventions. Chapter 3 analyzes the factors that drive the creation of technological novelty, with a particular focus on the role of global cities and how their concentration of R&D activities, technological specialization, and international collaboration jointly influence the emergence of new technologies. Chapter 4 investigates how the scientific content of new technologies influences the concentration patterns of innovative activities along their technological trajectories, showing that high scientific content is negatively associated with the concentration of innovative activities. Collectively, these three chapters advance our understanding of the complex and multifaceted nature of technological novelty, propose new insights into the mechanisms that drive technological change, and offer empirical evidence with important implications for research and innovation policies.