Human-made material stocks accumulating in buildings, infrastructure, and machinery play a crucial but underappreciated role in shaping the use of material and energy resources. Building, maintaining, and in particular operating in-use stocks of materials require raw materials and energy. Material stocks create long-term path-dependencies because of their longevity. Fostering a transition toward environmentally sustainable patterns of resource use requires a more complete understanding of stock-flow relations. Here we show that about half of all materials extracted globally by humans each year are used to build up or renew in-use stocks of materials. Based on a dynamic stock-flow model, we analyze stocks, inflows, and outflows of all materials and their relation to economic growth, energy use, and CO2 emissions from 1900 to 2010. Over this period, global material stocks increased 23-fold, reaching 792 Pg (±5%) in 2010. Despite efforts to improve recycling rates, continuous stock growth precludes closing material loops; recycling still only contributes 12% of inflows to stocks. Stocks are likely to continue to grow, driven by large infrastructure and building requirements in emerging economies. A convergence of material stocks at the level of industrial countries would lead to a fourfold increase in global stocks, and CO2 emissions exceeding climate change goals. Reducing expected future increases of material and energy demand and greenhouse gas emissions will require decoupling of services from the stocks and flows of materials through, for example, more intensive utilization of existing stocks, longer service lifetimes, and more efficient design. Significance A large part of all primary materials extracted globally accumulates in stocks of manufactured capital, including in buildings, infrastructure, machinery, and equipment. These in-use stocks of materials provide important services for society and the economy and drive long-term demand for materials and energy. Configuration and quantity of stocks determine future waste flows and recycling potential and are key to closing material loops and reducing waste and emissions in a circular economy. A better understanding of in-use material stocks and their dynamics is essential for sustainable development. We present a comprehensive estimate of global in-use material stocks and of related material flows, including a full assessment of uncertainties for the 20th century as we analyze changes in stock-flow relations.