The line is famous especially for its charming course through the Upper Danube Nature Park (Naturpark Obere Donau), and is particularly attractive to bicycle tourists.

The railway touches the border of the Swabian Jura (Schwäbische Alb) between Allmendingen and Blaustein, and meets its eponymous river again at the line's terminus in Ulm.

The Donauradweg (Danube Bicycle Trail), which also goes from Donaueschingen to Ulm, and continues on to Vienna, runs parallel to the line for much of the way.

However, the importance of this pan-regional East-West connection has been markedly reduced in recent times, primarily due to the relatively low average speed on the line.

This low speed is caused by the limitations imposed by the single track, which means often lengthy halts at node stations, and required stops at crossing points.

In addition, in 2003 the Deutsche Bahn discontinued the Kleber-Express, which had used large portions of the Danube Valley Railway since 1954 to make a daily direct trip between Munich and Freiburg.

Especially the borders between the states of Baden, Württemberg, and the Province of Hohenzollern, which became part of Prussia in 1850, made such comprehensive railway planning difficult.

In just the section between Mengen in Württemberg and Immendingen in Baden, the Danube Valley Railway crosses state borders a total of ten times.

In 1861, 17 of these committees published a memorandum, which argued for the construction of a line from Ulm via Ehingen, Mengen, Meßkirch, and Singen to Schaffhausen in Switzerland, with a connection to Tuttlingen as well as to the Black Forest Railway (Baden), which was still in its planning phase at the time.

A connection between Ulm and Vienna already existed in the 1860s, and since Paris was already connected to Chaumont, Haute-Marne, closing the gap via construction of a railway from Ulm along the Danube to Donaueschingen, then further through the Schwarzwald to Freiburg, and across the Rhine river and the Vosges mountain range to Chaumont, found proponents amongst the committees along the Danube, and other parties, as the shortest route between Paris and Vienna.

However, not only were there major topographical issues, which were difficult to solve given the knowledge of the day, but the many border crossings necessary to build this railway also added to the list of problems with the concept.

Württemberg started with plans on a smaller scale, and, after negotiations with Baden and Prussia, received the right to build a railway to Sigmaringen in Hohenzollern, as well as to connect to the rail network of the state of Baden via the Hegau-Ablach Valley Railway in Mengen, which meant a connection to the western edge of the Bodensee.

On 28 April 1865, the legislative body (Landtag) of the state of Württemberg passed into law a bill to construct a railway from Ulm along the rivers Blau, Ach, and Schmiech to Ehingen, and further along the Danube to Sigmaringen.

An alternative route, which would have been much shorter and less expensive, and which would have branched off the already extant Südbahn at Erbach and followed the course of the Danube, was dropped in favour of a railway that would connect the towns of Blaubeuren und Schelklingen to the rail network.

For the construction of the numerous tunnels and bridges across the Danube, the Royal Württemberg State Railways in particular hired workers from Italy.

Württemberg, which was following the progress of the Black Forest Railway construction with great interest, now formulated the goal to connect their rail network to the new line in Baden.

However, building an extension to the Danube Valley Railway from Sigmaringen to the connection point in Immendingen in Baden, which would have meant the early completion of the line, was not in the plans.

The section of the Danube Valley Railway between Tuttlingen and Immendingen therefore saw much less traffic, and has been kept as a single-track rail line to today.

In December 1944, Allied bomber squadrons completely destroyed Ulm Hauptbahnhof, as well as the nearby shunting yard at Söflingen.

The Deutsche Bundesbahn did modernize some of the signaling equipment, but also removed many of the passing tracks, and closed the shunting yard at Söflingen as well as several stations experiencing reduced passenger numbers.

In 2003, the section between Immendingen and Fridingen was integrated into the Ringzug network, which meant an improvement in service for the western part of the Donautalbahn.

In the section between Munderkingen and Ulm, additional trains run every hour as line RS 3 of the Danube-Iller Regional S-Bahn, stopping at all stations, and operated by the Hohenzollerische Landesbahn.

Agricultural equipment manufactured at the factory of the company CLAAS in Bad Saulgau make their way via Mengen across the Donautalbahn.

For the RegionalExpress trains running between Konstanz and Offenburg, which travel on the Donautalbahn between Donaueschingen and Immendingen, the DB AG uses electric locomotives of the class 146, and double-decker cars.

Between Sigmaringen and Ulm, the hope is that with the use of tilting technology trains, top speeds of 160 km/h may be reached, which would connect the two points with a trip time of under one hour.

A study by the name Bodan Rail 2020, which looked into the potential provided by rail service in the greater Bodensee area, namely between southern Germany, the Vorarlberg region in Austria, the north of Switzerland, and Liechtenstein, predicted the tripling or even quadrupling of passenger counts on the Donautalbahn section between Tuttlingen and Ulm, if trip times were reduced by the use of tilting technology.