The church of Sant'Ignazio had remained unfinished with bare ceilings even after its consecration in 1642. Disputes with the original donors, the Ludovisi, had prevented the completion of the planned dome. Pozzo proposed to resolve this by creating the illusion of a dome, when viewed from inside, by painting on canvas. It was impressive to viewers, but controversial; some feared the canvas would soon darken.
Born in Trento (then under Austrian rule), he studied Humanities at the local Jesuit High School. Showing artistic inclinations he was sent by his Father to work with an artist; Pozzo was then 17 years old (in 1659). Judging by aspects of his early style this initial artistic training came probably from Palma il Giovane. After three years he came under the guidance of another unidentified Painter from the workshop of Andrea Sacchi who appears to have taught him the techniques of Roman High Baroque. He would later travel to Como and Milan.
On 25 December 1665, he entered the Jesuit Order as a lay brother. In 1668, he was assigned to the Casa Professa of San Fidele in Milan, where his festival decorations in honour of Francis Borgia recently canonised (1671) met general approval. He continued artistic training in Genoa and Venice. His early paintings attest the influence of the Lombard School: rich colour, graphic chiaroscuro. When he painted in Genoa the Life of Jesus for the Congregazione de' Mercanti, he was undoubtedly inspired by Peter Paul Rubens.
Pozzo's artistic activity was related to the Jesuit Order's enormous artistic needs; many Jesuit churches had been built in recent decades and were devoid of painted decoration. He was frequently employed by the Jesuits to decorate churches and buildings such as their churches of Modena, Bologna and Arezzo. In 1676, he decorated the interior of San Francis Xavier church in Mondovì. In this church one can already see his later illusionistic techniques: fake gilding, bronze-coloured statues, marbled columns and a trompe-l'oeil dome on a flat ceiling, peopled with foreshortened figures in architectural settings. This was his first large fresco.
In Turin (1678) Pozzo painted the ceiling of the Jesuit church of SS. Martiri. The frescoes gradually deteriorated through water infiltration. They were replaced in 1844 by new paintings by Luigi Vacca. Only fragments of the original frescoes survive.
Meanwhile he continued painting frescoes and illusory domes in Turin, Mondovì, Modena, Montepulciano and Arezzo. In 1681 he was asked by Cosimo III de' Medici, Grand Duke of Tuscany to paint his self-portrait for the ducal collection (now in the Uffizi in Florence). This oil on canvas has become a most original self-portrait. It shows the Painter in a diagonal pose, showing with his right index finger his illusionist easel painting (a trompe-l'oeil dome, perhaps of the Badia church in Arezzo) while his left hand rests on three books (probably alluding to his not-yet published treatises on perspective). The painting was sent to the duke in 1688. He also painted scenes from the life of St Stanislaus Kostka in the saint's rooms of the Jesuit novitiate of Sant'Andrea al Quirinale in Rome.
His masterpiece, the illusory perspectives in frescoes  of the dome, the apse and the ceiling of Rome's Jesuit church of Sant'Ignazio (illustrations right and below) were painted between 1685–1694 and are emblematic of the dramatic conceits of High Roman Baroque. For several generations, they set the standard for the decoration of Late Baroque ceiling frescos throughhout Catholic Europe. Compare this work to Gaulli's masterpiece in the other major Jesuit church in Rome, Il Gesù.
There are a few architectural designs in his book Perspectiva pictorum et architectorum, indicating that he didn't make any designs before 1690. These designs were not realized, but the design for the S. Apollinare church in Rome was used for the Jesuit church of San Francesco Saverio (1700–1702) in Trento. The interior of this church was equally designed by Pozzo.
Pozzo published his artistic ideas in a noted theoretical work, entitled Perspectiva pictorum et architectorum (2 volumes, 1693, 1698) illustrated with 118 engravings, dedicated to Emperor Leopold I. In it he offered instruction in painting architectural perspectives and stage-sets. The work was one of the earliest manuals on perspective for artists and Architects and went into many editions, even into the 19th century, and has been translated from the original Latin and Italian into numerous languages such as French, German, English and, Chinese thanks to Pozzo's Jesuit connection.
In 1694 Andrea Pozzo had explained his illusory techniques in a letter to Anton Florian, Prince of Liechtenstein and ambassador of Emperor Leopold I to the Papal Court in Rome. Recommended by Prince Liechtenstein to the Emperor, Andrea Pozzo, on the invitation of Leopold I, moved in 1702 (1703?) to Vienna.There he worked for the sovereign, the court, Prince Johann Adam von Liechtenstein, and various religious orders and churches, such as the frescoes and the trompe-l'oeil dome in the Jesuit Church. Some of his tasks were of a decorative, occasional character (church and theatre scenery), and these were soon destroyed.
In 1695 he was given the prestigious commission, after winning a competition against Sebastiano Cipriani and Giovanni Battista Origone, for an altar in the St. Ignatius chapel in the left transept of the Church of the Gesù. This grandiose altar above the tomb of the saint, built with rare marbles and precious metals, shows the Trinity, while four lapis lazuli columns (these are now copies) enclose the colossal statue of the saint by Pierre Legros. It was the coordinated work of more than 100 Sculptors and craftsmen, among them Pierre Legros, Bernardino Ludovisi, Il Lorenzone and Jean-Baptiste Théodon. Andrea Pozzo also designed the altar in the Chapel of St Francesco Borgia in the same church.
In 1697 he was asked to build similar Baroque altars with scenes from the life of St Ignatius in the apse of the Sant'Ignazio church in Rome. These altars house the relics of St. Aloysius Gonzaga and of St. John Berchmans.
Pozzo was best known for his grandiose frescoes using the illusionistic technique called quadratura, in which architecture and fancy are intermixed. His masterpiece is the nave ceiling of the Church of Sant'Ignazio in Rome. Through his techniques, he became one of the most noteworthy figures of the Baroque period. He is also noted for the architectural plans of Ljubljana Cathedral (1700), inspired by the designs of the Jesuit churches Il Gesù and S. Ignazio in Rome.
At about the same time, between 1701 and 1702, he designed the Jesuit churches of San Bernardo and Chiesa del Gesù in Montepulciano. But his plans for the last church were only partly realized.
His most significant surviving work in Vienna is the monumental ceiling fresco of the Hercules Hall of the Liechtenstein garden palace (1707), an Admittance of Hercules to Olympus, which, according to the sources, was very admired by contemporaries. Through illusionistic effects, the architectural painting starts unfolding at the border of the ceiling, while the ceiling seems to open up into a heavenly realm filled with Olympian gods.
He died in Vienna in 1709 at a moment when he intended to return to Italy to design a new Jesuit church in Venice. He was buried with great honours in one of his best realisations, the Jesuit church in Vienna. Agostino Collaceroni was also a pupil.
His brother, Giuseppe Pozzo, a Discalced Carmelite friar in Venice, was also a Painter. He decorated the high altar of the Church of the Scalzi in that city during the last years of the 17th century.