The palace, erected on a large plot of land located just outside the Vilnia Gate on the edge of the suburb of Lukiszki, a private juridiction of the family of the coat of arms of Trąby, was called Januszowski after its creator Janusz Radziwiłł. The seat was situated on the slope of a hill (107 m above sea level), today illegible in the structure of the city, in the street leading to the bridge over the Neris, at the back of a Lutheran chapel and hospital with a cemetery.

Originally, this area was occupied by the manor house belonging to Jan Radziwiłł (1492- 1542), starosta of Samogitia, who was inherited by his daughter Petronela (d. 1564/67) married to Stanislaw Dowojna (d. 1573). However, the estate was taken over, not very legally, by her sister Anna (d. 1600), married to Stanislav Kishka (d. 1554), Voivode of Vitebsk. In 1574, she sold the wooden manor to Hetman Krzysztof "Piorun" Radziwiłł, who, it seems, abolished the old residence and began building a new one in its place or next to it "at great expense". Writing his will in 1599, he expressed confidence that whichever son received the realty would be "content" with it. He also recommended that "as the most splendidly built wood [...] a manor house near the Wilejska gate".

The Grand Hetman managed to complete the work on the new residence, and the manor house and garden fell to Krzysztof II (1585-1640), his younger son. This most influential dissenter in the Rzeczpospolita skilfully combined public activity with the care of a large group of literati and numismatic collecting. His son Janusz, educated and familiar with the circles of the European elite, quite quickly took over part of the Łukiszki estate. An accomplished dancer with impeccable manners, he was a collector of curiosities and books, but also an accomplished collector of paintings, trying his hand at this. At the same time, he displayed above-average courage on the battlefield, sought out quarrels under the influence of alcohol, and dealt cruelly with rebellious Cossacks.

Janusz Radziwiłł began the construction of the palace after 2 February 1638, when - against his family and his father's apparent reluctance - he married a Catholic woman, Catherine of the Potocki family (1619-1642), through her mother Maria of the Mohyl family, related to the family which sat on the thrones of Moldavia and Wallachia. The residence of the Grand Hetman of Lithuania and Voivode of Vilnius became the most magnificent residence of the Radziwills in Vilnius, and he himself was already the most powerful Lithuanian magnate at the time, with ambitions exceeding national politics. He enjoyed living and officiating in the palace as much as his duties allowed, often receiving guests.

The Januszowski Palace was built to a design by Costante Tencalla. The architect was a pupil and collaborator of Carlo Maderna in Rome, the builder of the Chapel of St Casimir at Vilnius Cathedral and the creator of the Church of the Discalced Carmelites of St Teresa. Although he designed the palace, Tencalla did not supervise the construction, being involved in the Warsaw investments of King Władysław IV. The construction was supervised by Jan Ulrich, who worked on another of Tencalla's works in Vilnius - St Teresa's Church, but also carried out work for Janusz Radziwill in Kėdainiai. Wilhelm Pohl and the Lutheran Adam Beier, a locksmith, also took part in the construction.

The seat was destroyed and looted during the Moscow occupation. Despite the rebuilding undertaken by its next owner, Boguslav Radziwill, by the end of the 17th century it had lost its importance and in the following century it gradually declined and was later demolished almost in its entirety. Only one pavilion and part of the north-east wing have survived to this day. The north-west pavilion was reconstructed and the north wing was extended after 1984. The building now houses Radvilų rūmų dailės muziejus, a branch of Lietuvos nacionalinis dailes muziejus. As of 2019, work is underway to expand the Radziwill residence for museum purposes.

This is because we have two reliable iconographic sources showing the palace. The first is a medal minted in 1653 by Sebastian Dadler (1586-1657) on the occasion of Janusz Radziwill's assumption of the Vilnius province, and the second is a map of Vilnius by Georg Max von Fürstenhoff from 1737.

On this basis, it can be concluded that the palace consisted of five three-storey pavilions with a mezzanine, which were connected by lower wings into a horseshoe. The front pavilions were connected by a low wall with two gates from Wileńska Street, and the whole complex was enclosed by an additional fence with two towers. The irregularly shaped grounds to the north and east contained gardens. The former was representative and functional, and opened onto it by a two-storey loggia of the northern wing covered with a separate flat roof. It should be noted that the palace had interesting spatial solutions in which diagonal axes were accentuated. Two viewpoints were also introduced. One straight ahead from the square created in front of the residence, and the other on the side at the exit from the city towards Vilnius gate.