It runs from Hauptbahnhof in Mitte eastwards through Alexanderplatz, Friedrichshain, Lichtenberg and Friedrichsfelde, surfaces in Biesdorf-Süd to pass Kaulsdorf and Hellersdorf above ground and finally reaches city limits at Hönow.

Line U5 connects Moabit with the large housing estate of Hellersdorf and the Brandenburg town of Hönow, but ends just outside the eastern city limits of Berlin.

It begins at Berlin Hauptbahnhof (central station) and heads southeast under the Spree river, the Spreebogenpark and the Platz der Republik to Brandenburg Gate.

It crosses Köpenicker Straße at Elsterwerdaer Platz station and a little later the street of Alt-Biesdorf, which forms part of both federal highways B 1 and B 5.

In 1910, the Elevated Railway Company changed its plans: U-Bahn line E would now pass under Alexanderstraße so that it could connect with the already approved section between Spittelmarkt and Schönhauser Allee.

The Elevated Railway Company originally planned to run line E along a section of Landsberger Allee that no longer exists from Alexanderplatz to Büschingplatz (where Mollstraße now connects to Platz der Vereinte Nationen), where a station would be built.

In 1925, the city of Berlin received a suggestion from the private sector to insert a 180-metre (590 ft)-long curve between Alexanderplatz and the current Schillingstraße station, so that it would run through Große Frankfurter Straße and not through Büschingplatz as planned.

There was also another change in planning that provided for line E not to end at Frankfurter Allee station, but to continue to Friedrichsfelde, because there was an area available there for a workshop.

After the Second World War, plans emerged to extend the line to Tierpark Berlin, a new zoo established in 1955 at Friedrichsfelde Palace.

When apartments were later built in the area of the zoo, the plan was taken up again, especially since the closure of the tram line on the street of Alt Friedrichsfelde as a result of the construction of the road bridge over Lichtenberg station had created a gap in the network.

Due to a lack of utilisation of the pile-driving capacity of the civil engineering VEB, construction began illegally at the Tierpark station, because the directors of the civil engineering company and the Berliner Verkehrsbetriebe (Berlin transport company; BVB) had carried out the first pile driving on 19 September 1969.

[7] To enable the tunnel shell, which had been damaged in the fire, to be restored quickly, a large number of precast concrete parts intended to be installed in the line extension in Friedrichsfelde were transferred from there.

At the beginning of the 1980s, the working groups of the Ministry of Transport of the GDR and the city council of Berlin investigated the construction of a rapid transit connection in the Kaulsdorf and Hellersdorf area.

It was also expected that expensive work to widen the railway embankment of the VnK route would be necessary and noise protection measures would have to be installed in Biesdorf Süd.

Old bridges located near Elsterwerdaer Platz, above Köpenicker Straße and above what is now the B 1 / B 5 highway had to be demolished and replaced with new ones to allow the widening of both roads.

[10] Track laying began in mid-February 1987, when the earthworks and the creation of the ballast formation had been completed on various sections of the line.

More than 12 kilometres (7.5 mi) were required just for the multiple relocations of S-Bahn and long-distance train tracks near today's Wuhletal station.

For this purpose and for the supply of material, an alternative construction connection point was established on the Berlin-Rummelsburg–Biesdorfer Kreuz Südwest line.

The opening ceremony took place at Elsterwerdaer Platz station with brass band music and speeches by leading party and state officials.

This time the opening ceremony took place at Tierpark station with the politician Günter Schabowski, several government ministers, the first secretary of the central council of the FDJ Eberhard Aurich, the mayor Erhard Krack and other officials.

Along its route it serves new U-bahn stations at Berliner Rathaus, Museumsinsel and Unter den Linden, with the last providing an interchange with line U6.

Between January 2003 and December 2004, reconstruction was conducted between Alexanderplatz and Friedrichsfelde in order to repair damage dating back to World War II.

The lighting has been renewed and made brighter, the technology has been brought up to date, the plaster has been extensively renovated and the walls have been clad in a vandalism-proof surface with enamelled sheet steel.

Equipping all stations with elevators to make them fully accessible is not planned until the lift program is completed on the rest of the metro network.

In the long term, there are plans to extend the line from Berlin Hauptbahnhof, via Turmstraße and Jungfernheide to Flughafen Tegel.

This plan was postponed due to the route being too long, the closure of Tegel Airport, and Berlin's poor fiscal situation.

An addition to the plan is an extension towards Rathaus Reinickendorf via Cité Pasteur Nord, Scharnweberstraße, and Eichborndamm.

The possibility of extending the tram line to Cité Pasteur Nord, Scharnweberstraße and Eichborndamm to Rathaus Reinickendorf remains in the vision stage.

Plans were revived in March 2023 under the "Express Metropolis Berlin", the route remains the same as before the U5 extension was cancelled in September 2016.