On 2 October 1832 (his birthday), King Charles Albert of Savoy inaugurated the royal gallery at the Palazzo Madama, containing 365 paintings.

In 1865, Massimo d'Azeglio had the collection transferred to Guarino Guarini's Palazzo dell'Accademia delle Scienze (1679) where it stood until 2012 before it was moved to the current location.

On 4 December 2014, in the presence of the Italian minister of culture, the "Manica Nuova" of Palazzo Reale (New Wing of the Royal Palace) was officially opened.

The gallery is based on a brand new museum project conceived and developed by the superintendent Edith Gabrielli (for the scientific part) together with Studio Albini Associati (staging).

The collection includes works by Netherlandish artists such as Gerrit Dou, Jan van Eyck, Rogier van der Weyden (side panels of the Annunciation Triptych), Jan van Huchtenburg, Hans Memling (Scenes from the Passion of Christ), Rembrandt, and Anthony van Dyck (Portrait of the Three Eldest Children of Charles I), as well as paintings by Italian artists such as Duccio di Buoninsegna (Gualino Madonna), Macrino d'Alba, Sandro Botticelli, Filippino Lippi (Three Angels and Young Tobias), Bernardo Daddi, Fra Angelico, Piero del Pollaiuolo, Agnolo Bronzino, Bernardo Bellotto, Giovanni Canavesio, Orazio Gentileschi (Annunciation), Andrea Mantegna, Girolamo Savoldo, Giovanni Battista Tiepolo, Gaudenzio and Defendente Ferrari, Giovanni Bellini, Guercino, Francesco Cairo, Sebastiano Ricci, Giovanni Martino Spanzotti, Titian, Paolo Veronese, and Tintoretto, and the Frenchman Pierre Subleyras.