The Larry McMurtry Collection contains multiple typescript manuscript drafts of the novels Leaving Cheyenne, The Last Picture Show, Moving On, Somebody's Darling, Cadillac Jack: A Novel, The Desert Rose, Lonesome Dove, and Texasville, plus manuscript notes and publisher's copies related to some of these works. The collection also contains the typescript manuscripts and first galley proofs for the book of essays In a Narrow Grave.

The McMurtry Collection includes a screenplay for Hud (the film adaptation of McMurtry's Horseman, Pass By), and the screenplay for the John Cougar Mellencamp film project Falling from Grace (titled Ridin' the Cage and Indiana Moon in these drafts). Also in the collection are scripts for the cable television movies Montana and Memphis (titled September, September in these drafts), which was adapted from a novel by Shelby Foote and co-written with Cybil Shepherd. Many scripts are included which have not been produced, such as Cantrell and Somebody's Darling, which credits Diane Keaton as co-writer in some drafts.

The collection includes a large amount of correspondence. There are three major sections of correspondence –- from McMurtry to his friend and Bookman store owner Grace David, from McMurtry to his friend Mike Kunkel, and from Harper and Row editor John Leggett to McMurtry. The Leggett correspondence concerns changes to the manuscripts for Horseman, Pass By and Leaving Cheyenne. Other correspondence includes that from McMurtry to book dealer Miles Karpilow.

A wide-ranging collection, the Larry McMurtry Papers also includes short prose and poetry, numerous literary reviews written by McMurtry, news articles about his books and films, notes on projects considered, transcriptions of taped interviews used as research for The Desert Rose, scripts which McMurtry worked on as an advisor without receiving credit, photographs, and other miscellaneous documents.

The collection is organized into six major series: McMurtry’s Writings, Correspondence, Other Projects, Works by Other Authors, Photographs, and Miscellaneous. The first series, McMurtry’s Writings, contains the bulk of the collection contents. This series is divided into three sub-series: Novels, Scripts, and Other Writings. Most individual works are given their own sub-series, and these are arranged alphabetically. The Correspondence, Other Projects, and Miscellaneous series have also been subdivided.

Additional manuscript material of Larry McMurtry is held at the University of North Texas in Denton, Southwest Texas State University in San Marcos, and Rice University in Houston. The Texana Collection of the Willis Library at the University of North Texas contains some of McMurtry's student literary submissions and papers, plus typescript manuscripts of Horseman, Pass By and Leaving Cheyenne. The Southwestern Writers Collection at the Alkek Library of Southwest Texas State University includes the screenplay and many other materials from the television mini-series Lonesome Dove, and a typescript of the 1972 screenplay Streets of Laredo, on which the Lonesome Dove novel was based. The Woodson Research Center of Fondren Library at Rice University has two collections of papers documenting McMurtry’s collaboration with Diana Ossana. These collections contain drafts, correspondence, and related materials.