This project promotes investigation of poems within early modern manuscripts as an effective means to illuminate contemporary perspectives on writers and their works. With few methods available for accessing Renaissance readers' explications of multivalent and frequently encoded texts, I emphasize analysis of certain literary manuscripts as a method for considering how readers encountered, grouped, and interpreted verse. Interpretive evidence often appears in elements such as the sequence of items chosen for inclusion, paratexts, titles, ascriptions, even watermarks. Extant manuscripts containing copies of poems by Donne, who (like many contemporary poets) composed verse almost exclusively for a manuscript medium, prove fruitful for exploring this thesis because more of his verse circulated in manuscript than any other Renaissance poet's. The first chapter provides a methodology for such study, while the remaining chapters demonstrate how this research perspective alters our understanding of Donne's satiric, religious, and dubious verse. In the second chapter, study of components such as the title-page and scripts in a composite Folger collection suggests that at least one seventeenth-century reader interpreted Metempsychosis as a satire on court favorites, specifically Elizabeth I's advisor Robert Cecil, thus offering insight into one of Donne's most confusing poems. The third chapter reveals that investigation of apocrypha within original artifacts can reshape authorial canons. I argue that "Psalme 137," a verse translation that editor Herbert Grierson attributed to Francis Davison, actually belongs to Donne. Through study of a British Library miscellany, the fourth chapter addresses the critically contested matters of manuscript attributions and Renaissance attention to "authorship" and demonstrates how analysis of bibliographic contexts for one poet's lyrics can offer insights regarding other poets--in this case, Francis Beaumont, Thomas Carew, Sir Walter Ralegh, and John Fletcher, likely author of an important elegy on Richard Burbage. The chapter also analyzes a significant and hitherto unidentified verse epistle likely composed for Elizabeth I by Henry Wriothesley, third earl of Southampton. Generally, this dissertation depicts ways in which arrangement and structure of certain seventeenth-century manuscripts reveal clues to contemporary audiences' perceptions of Donne and his fellow poets and interpretations of texts, enriching modern exegesis as well.