[2] The railway line was designed under the Austro-Hungarian Empire in the mid-19th century to ensure rapid and safe transport between Tyrol and northern Italy, especially Lombardy–Venetia.

The design of this section was approved on 10 July 1853 by the engineer Alois Negrelli, an employee of the Südbahn, known for having built other Alpine railway lines and for developing a project of the Suez Canal.

[3] Despite the loss of Veneto in the Third Italian War of Independence and its consequent shift of the border between Italy and Austria to Borghetto on the current boundary of Trentino and Verona in October 1866, the upper section from Bolzano/Bozen to Innsbruck was incomplete.

In preparation for the proposed Brenner Base Tunnel, the Innsbruck bypass was completed in 1994 to improve access to the Lower Inn Valley railway.

The bypass consists of a 12.75-kilometre (7.92 mi) tunnel (Austria's longest) and aims to remove the bulk of the freight train traffic from Innsbruck.

Following a sharp increase in freight traffic through the Brenner Pass (largely on road), the railway is currently considered to have insufficient capacity.

Moreover, its steep grades, tight radius bends and the need to change locomotive engines at Brenner due to two different electrical systems as used in Austria and Italy mean that the average travel speed is low.

In recent years the introduction of multicurrent rolling stock, which can be run on both the Austrian and Italian networks, has made it possible, at least in principle, to avoid locomotive changes.