The sixteenth century was a golden age for botany, a time when numerous naturalists devoted themselves to the study and documentation of plant diversity. A very prominent figure among them was the German physician, botanist, and traveler Leonhard Rauwolf (1535?–1596), famous for his travel account and luxurious book herbarium containing plants from the Near East. Here, we focus on the less studied, early book herbaria of Rauwolf. These form a three-volume plant collection bound in leather and gold, which contains over 600 plants that Rauwolf collected between 1560 and 1563 in S. France and N. Italy when he was a student of medicine. We show the botanical value of Rauwolf’s early book herbaria, exemplified by two exotic American specimens, namely one of the oldest surviving specimens of tobacco ( Nicotiana rustica), collected in Italy, and the oldest known French record of prickly pear ( Opuntia ficus-indica). These well-preserved specimens indicate that Rauwolf was eager to collect exotic plants already in his early botanical steps. We further discuss Rauwolf’s professional botanical network during his student years and suggest that the famous Swiss botanist Johann Bauhin (1541–1613), friend and companion of Rauwolf during his field excursions and their medical studies in Montpellier, has played a significant role in the compilation of this precious historical plant collection. We also show that Leonhart Fuchs (and not Carolus Clusius) extensively annotated the three book herbaria. Finally, we reconstruct the story of making of the book herbaria, as evidenced through observations of paper watermarks and handwritten texts in the book volumes, and show that all four book herbaria of Rauwolf were probably bound between 1577 and 1582.