Built from 1843 to 1855 by order of King Frederick William IV of Prussia in Neoclassical and Renaissance Revival styles, it is considered as the major work of Friedrich August Stüler.

After suffering damage in World War II and decay in East Germany, it was restored from 1999 to 2009 by David Chipperfield.

The soft, spongy soil around the River Spree means that buildings in the central area of Berlin require deep foundations.

With its new industrialized building procedures and its use of iron construction, the museum plays an important role in the history of technology.

The poor quality of the ground at the building site became apparent quickly, when the workers discovered deposits of diatomaceous earth just below the surface.

An auxiliary railway transported building materials from the street just west across the River Spree, Am Kupfergraben, to the steam engine-driven elevator.

As soon as the respective areas were completed, the installation of the collection began, until the museum was finally opened in 1855 to the public, although work on parts of the interior decoration, in particular the wall frescos in the stairway, continued until 1866.

However, because of a change in curatorial priorities in favour of original works of art, it was handed over between 1916 and 1920 (with the exception of the largest statues) to the Berlin University, where it was destroyed to a large extent during World War II.

In the adjacent areas of the ground floor, suspended ceilings were added to produce modern, neutral display rooms by covering the original decorations.

In June 2003 the Federal Government Commissioner for Cultural and Media Affairs [de], Christina Weiss [de], said on the occasion of the ceremony for the commencement of reconstruction of the museum that the master plan had "nearly squared the circle: to emphasize the buildings as a historical inheritance, to logically direct the flow of the host of visitors, and to make ready... a modern infrastructure."

The "Cube", which cost about €60 million, was under a planning freeze, which Chipperfield saw as endangering progress on the Neues Museum, according to ZDF, the Second German Television channel.

In view of the total cost of the Museum Island master plan, estimated to be €1.5 billion, the controversy over the €60 million for the "Cube" appeared disproportionate not only to the architect.

A March 2006 report on ZDF commented, "if the planning freeze is not lifted by the end of the year, the "Cube" cannot be completed in time.

The northwest wing and the south-east façade, which were completely destroyed in the war, have been reconstructed according to Chipperfield's plan, in a manner close to their original layout in the museum building.

[6] A group called the Society of Ancient Berlin requested UNESCO in 2008 to put the Museum Island on the list of World Heritage Sites that are at danger of losing their status, seeing Chipperfield's architectural concept involving complete reconstructions as a form of cultural destruction.

[8] By contrast, the design was acknowledged in 2011 when David Chipperfield Architects in collaboration with Julian Harrap were awarded the European Union Prize for Contemporary Architecture.

Portions of another major collection, artifacts from the Stone Age and later prehistoric eras from the Museum of Pre- and Early History, are on display.

The architectural dialogue between the two buildings is now evident, representing the culmination of a process that began when the Neues Museum reopened in 2009.