The first section from Halle to Weissenfels was opened by the Thuringian Railway Company (Thüringische Eisenbahn-Gesellschaft) on 20 June 1846.

[3] Since May 1995, the line has been electrified and the maximum speed is 160 km/h in substantial parts,[5] with the exception, for example, of Erfurt and Bebra stations and the Hönebach Tunnel (983 m long, 90 km/h).

The first stage of the reconstruction, beginning in October 2005, ran from the southern approach to Halle to the exit from the high-speed line to the city.

[11] The Erfurt–Eisenach section is to be upgraded by December 2019 for speeds of 200 km/h over a length of about 54 km as part of German Unity Transport Project no.

In addition, the subgrade is to be improved over a length of four kilometres along the Leina Canal and two bridges are to be rebuilt in Fröttstädt and Seebergen.

Modernisation, including the upgrade of the stations Schkopau and Bad Kösen for barrier-free access, is planned in the coming years with federal and state funds.

The Hessian section between Bebra and Eisenach has been operated by Cantus as NVV line R6 with Stadler Flirt electric multiple units (EMUs) since December 2006.

Line RB20 runs between Eisenach and Halle (Saale) and is managed by Nahverkehrssservicegesellschaft Thüringen (Thuringian local transport authority).

The services of the Thuringian Railway were tendered in 2012 as part of the Elektronetzes Saale-Thüringen-Südharz (Saale-Thuringia-South Harz Electric Network).

In addition, the combined RE3/RE7 express service runs from Würzburg via Schweinfurt and Suhl to Erfurt and, after a 20-minute stop, continues from there with a number change via Weimar and Gera to Altenburg or Elsterberg.

The first line (36) ran from Frankfurt via Erfurt and Halle to Berlin, with some services continuing to the Baltic coast.

Both InterRegio lines served in addition to the stops of the Intercity services, the stations in Bebra, Gotha, Naumburg and Weißenfels.

In 2004, IC 15 service was converted to ICE-T operation and integrated into line 50, which now ran hourly between Frankfurt (Main) and Dresden.

Basically, the timetable was provided a service every two hours, with all trains stopping in Eisenach, Gotha, Erfurt, Weimar and Naumburg, while an alternating service also ran every two hours but only stopped in Eisenach and Erfurt and as a result achieved the approximately 15 minute shorter running times of the tilting-train period.

Immediately south of Merseburg the line runs through the Leuna-Werke (where IG Farben produced synthetic oil during World War II and which is now a location of a Total oil refinery and numerous chemical factories) to Großkorbetha, where it meets the main line from Leipzig.

During the existence of the German Democratic Republic, this section of the line had great importance, especially for commuting from Halle-Neustadt to the chemical works in Leuna and Buna.

After the spa town of Bad Kösen, the Saal Railway branches to the south towards Jena, Saalfeld and Munich.

The line continues to the southwest past Saaleck, through a series of bends in the valley of the Ilm, which it crosses four times.

The 12 kilometre-long section was equipped with two additional tracks in 1910–1912 for freight traffic and a flying junction was built at Neudietendorf station towards Arnstadt on the Erfurt–Schweinfurt line.

On the forecourt of the station is the beginning of route of the Thuringian Forest Railway (Thüringerwaldbahn), an overland interurban tramway to Bad Tabarz via Waltershausen and Friedrichroda.

The line reached the watershed between the Weser and Elbe rivers shortly after Gotha, at the 141.8 km mark.

The line runs along the charming Hörsel valley between the Hörselberge range to the north and the Thuringian Forest to the south.

After the war, the Red Army used the northern part of the station to load and unload tanks for the nearby Kindel firing range until 1990.

[25] The line crosses the A 4, passes through the community of Wutha-Farnroda, where formerly the Ruhla Railway branched off, and finally reaches the city of Eisenach, which is the first Intercity-Express stop since Erfurt.

At Herleshausen the line passes through Hessian territory for seven km, before returning to Thuringia and continuing to Gerstungen.

The fact that the line crossed the Inner German border five-times during the division of Germany created security problems for the GDR.

For this reason, in the years 1961/1962, after the establishment of the Berlin Wall, a single-track detour line was built in East Germany, the Förtha–Gerstungen railway.

Early in the morning of 29 January 1962, the D 28 express train from Berlin to Eisenach was involved in an accident at Mechterstädt-Sättelstädt station.

The state-controlled GDR media concealed the incident and it was only mentioned in a three-line note in a local newspaper.

[27] On 23 June 1976 at about 17:25, the international express D 354, running from Berlin to Paris crashed at the western end of Eisenach station.