Pharmaceuticals have been detected at high concentrations in municipal solid waste (MSW) landfill leachates, which are recognized as an underestimated source of pharmaceutical residues in the environment. However, limited efforts have been made to characterize pharmaceuticals in MSW landfill refuse, which is also of significant concern given the potential long-term environmental impact. Herein, we excavated landfill refuse from six cells with landfill ages of 7−27 years in the largest MSW landfill in Shanghai (in each cell, landfill refuse was collected from different depths of 2−8 m) and analyzed samples for the presence of 55 pharmaceuticals, including antibiotics and non-antibiotics. The results reveal the presence of 42 pharmaceuticals in landfill refuse, with median concentrations ranging from 0.30 to 116 μg/kg. Antibiotic and non-antibiotic pharmaceuticals exhibited diverse concentration trends with age, related to changes in policy intervention and consumption over time. Different concentration variations of individual pharmaceuticals were observed in refuse samples excavated at different depths and positively correlated to their sorption ability. The mass of pharmaceuticals in the investigated landfill was estimated from the obtained concentrations to be 80−220 tons with 95% probability, based on Monte Carlo analysis. To the best of our knowledge, this study provides the first estimate of pharmaceutical mass in an MSW landfill. The results will be helpful for understanding the potential long-term environmental impact of pharmaceuticals in landfills.