The industrial sector is now undergoing digital revolution and upgrade, and it is of strategic significance to study how enterprise digitalization affects enterprise innovation. This paper develops a theoretical model of how digital transformation affects innovation in manufacturing enterprises, based on the resource-based view, network-embeddedness theory, and resource-complementarity theory. It then tests the mechanism and boundary conditions of the model, using data from a World Bank survey of Chinese enterprises. The study reveals how the degree of e-commerce embeddedness might partially mediate the effect of digital transformation on the innovation of manufacturing companies. Managerial human capital positively moderates the effect of digital transformation on manufacturing enterprises’ independent-R&D investment and product-innovation output. Employee human capital significantly and positively moderates the effect of digital transformation on manufacturing enterprises’ product-innovation output, while negatively moderating the effect of digital transformation on manufacturing enterprises’ cooperative-R&D investment. The conclusions can expand the relevant theoretical research on digital transformation and enterprise innovation, and also provide practical enlightenment for the digital transformation and upgrading of manufacturing enterprises.