In order to provide a theoretical foundation for the utilization of tailings as supplementary cementitious materials, the pozzolanic activity of muscovite—a typical mineral phase in tailings—before and after mechanical activation was investigated. In this study, significant pozzolanic activity of muscovite was obtained as a result of the structural and morphological changes that were induced by mechanical activation. The activated muscovite that was obtained after mechanical activation for 160 min satisfies the requirements for use as an active supplementary cementitious material, and the main characteristics of the pozzolana were as follows: median particle size (D50) of 11.7 μm, BET specific surface area of 28.82 m2 g−1, relative crystallinity of 14.99%, and pozzolanic activity index of 94.36%. Continuous grinding led to a gradual reduction in the relative crystallinity and an increase in the pozzolanic activity index due to the dehydroxylation reaction induced by mechanical activation, which occurred despite the fact that the specific surface area showed a decreasing trend when the grinding time was prolonged. Mechanically activated muscovite exhibited the capacity to react with calcium hydroxide to form calcium silicate hydrate, which is a typical characteristic of pozzolana. This experimental study provided a theoretical basis for evaluating the pozzolanic activity of muscovite using mechanical activation.