The Codex Azcatitlan is an Aztec codex detailing the history of the Mexica and their migration journey from Aztlán to the Spanish conquest of the Aztec Empire. The exact date when the codex was produced is unknown, but scholars speculate it was crafted some time between the mid-16th and 17th centuries. The name of this important Mexica pictorial manuscript was suggested by its first editor, Robert H. Barlow, who erroneously interpreted the anthill on page 2 as the glyph for “Aztlán.” In the Bibliothèque nationale de France, where it is housed, it is known as Histoire mexicaine, [Manuscrit] Mexicain 59–64.

The style of the codex combines traditional Mesoamerican artisanry with European Renaissance technique. Mexican historian Federico Navarrete [es] noted the use of European methods to depict the codex's content such as the use of three-dimensional objects. The master tlacuilo also uses overlapping images to create depth, as in European art. Figures in the codex also have a greater degree of movement than in prior manuscripts.

The codex's construction combines the pre-Columbian Aztec method of accordion-folding, but is bound in the two-page European style. Each of the 25 leaves, made of European paper, is about 21 centimeters (8.3 in) high and 28 centimeters (11 in) wide. The images within the codex flow across the surface of the pages until it runs out of space. In that event, the last image of the set is recreated exactly for the first image of the succeeding set. Inconsistencies in that flow seem to indicate that some of the pages are missing. The manuscript is also incomplete; color is sporadically used, and there are still draft lines and empty spaces.

This codex has two authors, or tlacuiloque [es], a master and an apprentice. The master laid out the entire narrative and then painted the more difficult and more important portions of the codex. The master observes Mesoamerican custom, most identifiable in his human figures, nearly always shown in profile, with angular faces looking to the right. The apprentice's figures, by contrast, use more curved lines and shadowing to better define the human body. He draws faces in profile until folio 9r, where a character looks directly at the observer. The master used bold and complete lines and coloration for his figures and glyphs.

One or both of the tlaquiloque may have known Antonio Valeriano, the pro-Tlateloco Governor of Tenochtitlan from 1573 to 1599. They may have also studied at the Colegio de Santa Cruz de Tlatelolco.

It appears that the master tlacuilo drew each set of specific year glyphs (Reed, Flint, House, Rabbit) in one session. This is alluded to by consistencies in form and inconsistencies in color by set. Once these were painted, he added the corresponding years in the Julian calendar, which in their forms resemble the glosses added to the codex later.

The first instances of work by the apprentice tlacuilo are found on folio 6v, as there appear houses shaded as per his method. He takes over completely until folio 12r, when the Mexica arrive at Tenochtitlan.

It is not known when the manuscript was created, or whether it was first painted and then bound, or vice versa. Historian María Castañeda de la Paz has proposed the second half of the 16th century as the window of time in which Codex Azcatitlan was authored. The writing of the glosses in Nahuatl suggests a date in the last third of the sixteenth century, but the glosses may not be contemporary with the drawings, since the glossarist did not always understand them correctly.