Giulio's drawings have long been treasured by collectors; contemporary prints of them engraved by Marcantonio Raimondi were a significant contribution to the spread of sixteenth-century Italian style throughout Europe.

The contemporaneous historian of the Renaissance, Giorgio Vasari (1511–1574), tells how Baldassare Castiglione was delegated by Gonzaga to procure Giulio to execute paintings as well as architectural and engineering projects for the duchy of Mantua.

Giulio sculpted the figure of Christ that is positioned above Castiglione's tomb in the church of Santa Maria delle Grazie, in Curtatone, near Mantua.

According to Vasari: When Charles V came to Mantua, Romano, by the duke's order, made many fine arches, scenes for comedies and other things, in which he had no peer, no one being like him for masquerades, and making curious costumes for jousts, feasts, tournaments, which excited great wonder in the emperor and in all present.

For the city of Mantua at various times he designed temples, chapels, houses, gardens, facades, and was so fond of decorating them that, by his industry, he rendered dry, healthy and pleasant places previously miry, full of stagnant water, and almost uninhabitable.

[5]He traveled to France in the first half of the sixteenth century and brought concepts of the Italian style to the French court of Francis I. Giulio designed tapestries as well.

In Act V, Scene II of The Winter's Tale, the statue of Queen Hermione that was described as coming to life during the play was identified by the bard as having been sculpted by "that rare Italian master, Julio Romano".

The project for the Villa Madama outside Rome, built by the future Medici Pope Clement VII was given to Giulio on Raphael's death.

The volutes of the Ionic capitals are repeated in the window surrounds between them: "The canonic orders here begin to be treated visually as independent from their structural purposes, and this liberation offered the architect new expressive possibilities.