The Main-Neckar Railway (German: Main-Neckar–Eisenbahn, MNE) is a main line railway west of the Odenwald in the Upper Rhine Plain of Germany that connects Frankfurt am Main to Heidelberg via Darmstadt, Bensheim and Weinheim. It was opened in 1846 and is one of the oldest railways in Germany.

The railway line is part of the networks served by the Rhein-Main-Verkehrsverbund and Verkehrsverbund Rhein-Neckar.

The Main-Neckar Railway was built and operated as a joint state railway company, known as a condominium railway (Kondominalbahn), by the Free City of Frankfurt, The Grand Duchy of Hesse-Darmstadt and the Grand Duchy of Baden.

The plans for the railway dated back to 1835. However, years went by until the three states involved agreed on routes and how it would be organised. Not until 1838 was a treaty for the construction of a Railway from Frankfurt to Mannheim via Darmstadt agreed. The Hessian Railway Company could not raise the required capital and it was then dissolved. There was a second treaty signed of 21 and 23 March 1843, which agreed to build the Main-Neckar line at government expense and—as a compromise between the interests of Mannheim and Heidelberg—located the line centrally in Friedrichsfeld where it joined the Mannheim–Heidelberg line of the Grand Duchy of Baden State Railway. Baden requested that the line be built to 1600 mm broad gauge but could not gain agreement for this. Responsibility for funding the project was in proportion to the length of the line in the three countries: Frankfurt: 6.9 km (4 mi), Hesse-Darmstadt: 49.4 km (31 mi) and Baden: 38.8 km (24 mi). All three governments were represented in the management of the Main-Neckar Railway in Darmstadt.

The construction of the line began in June 1843 on the Frankfurt section. The management of construction was carried out by municipal chief engineer Remigius Eyssen. On 16 April 1846, the first trial service ran from Darmstadt to Langen. The fare for this trip was 1 guilder and 6 kreuzers for first class, 48 kreuzers for second class, 33 kreuzers for third class and 21 kreuzers for fourth class.

The line was opened for the scheduled traffic in sections:

Until the Main-Neckar Bridge in Frankfurt (at the site of today's Friedensbrücke) was completed on opened to traffic on 15 November 1848, rail services ran into the Mainspitze depot and reversed to the old Sachsenhausen station. After the completion of the bridge over the Main the line ended in Main-Neckar station. The original temporary wooden bridge at Ladenburg was replaced by a stone arch bridge in 1848.

Since the Baden Mainline between Mannheim and Heidelberg was built with a broad gauge of 1600 mm and the Main-Neckar line with standard gauge of 1435 mm, additional track had to be built: from Friedrichsfeld to Heidelberg a second line ran next to the line of the Baden State Railway line. From Friedrichsfeld to Mannheim, the Baden State Railway built an additional standard gauge track at its own expense, although it was operated by the Main-Neckar Railway.