Developing evidence-based uses of herbal medicines and natural product-based drug discovery are two core aims of ethnopharmacology. This requires an understanding of the medicinal plants and the traditional medical knowledge associated with them which is a basis for cross-cultural comparison. The botanical drugs of traditional medical systems are still not understood well, even for well-known and widely respected traditions like Ayurveda. In this study, a quantitative ethnobotanical analysis was performed on the single botanical drugs included in the Ayurvedic Pharmacopoeia of India (API), presenting an overview on the medicinal plants of Ayurveda from perspectives of plant systematics and medical ethnobotany. Part-I of API includes 621 single botanical drugs, which are sourced from 393 species (323 genera in 115 families). Of these, 96 species yield two or more drugs, together accounting for 238 drugs. Taking the traditional concepts, biomedical uses and the pragmatic disease classification into account, therapeutic uses of these botanical drugs are sorted into 20 categories, which meet primary health demands. The therapeutic uses of the drugs sourced from the same species may differ considerably, but 30 of the 238 drugs are used in highly similar way. The comparative phylogenetic analysis identifies 172 species with high potential for specific therapeutic uses. This medical ethnobotanical assessment for the first time provides a comprehensive understanding on the single botanical drugs in API from the perspective of medical botany using an “etic” (scientist-oriented) approach. This study also highlights the importance of quantitative ethnobotanic methods in understanding traditional medical knowledge.