The Frankfurt-Hanau Railway Company (German: Frankfurt-Hanauer Eisenbahn Gesellschaft, FHE) was founded at the initiative of the Prussian consul general to the Free City of Frankfurt, Moritz von Bethmann and with the financial support of the Gebrüder Bethmann bank of Frankfurt and the Bernus du Fay bank of Hanau.

On 12 April 1843, the company received a preliminary construction permit from the Electorate of Hesse (Kurhessen), which was converted into a concession in 1844.

The original 16.4 km long track is located on the right, northern bank of the Main and was designed by the engineer Peter Johann Wilhelm Zobel.

There was opposition to building the line in Dörnigheim, where the village was divided from part of its fields by the railway, but did not receive a station.

A week after the opening the railway was affected by revolutionary events: a vote of the National Assembly on 16 September 1848 reversed its original rejection of the Armistice of Malmö on Schleswig-Holstein, leading to an attempted revolt of radical forces in Frankfurt.

Before the building of the line there was a government crisis in Hesse in 1852, because Elector Frederick William expected a bribe of 100,000 thalers from the Bernus du Fay bank before he would sign the appropriate license for the extension of the railway towards Aschaffenburg.

The Hessian Ludwig Railway (Hessische Ludwigs-Eisenbahn-Gesellschaft, HLB), which was established in the Grand Duchy of Hesse recognized the importance of the HLB for the expansion of railway services in the Rhine-Main region, particularly to the province of Upper Hesse (an exclave of the Grand Duchy), from the Rhine-Main area to Bavaria and via the Kinzig valley to Bebra.

The new line involved crossing the Frankfurt–Hanau railway at a junction about a kilometre east of the edge of Hanau's built-up area at the time.

On 1 April 1913, the line was extended by 2.38 km from the new East station via the Deutschherrn bridge over the Main to Frankfurt South.

A ramp from Seehofstrasse is followed by a flyover structure over the Main south bank line to Hanau, immediately after which federal highway 43 is crossed.

Northeast of Frankfurt-Mainkur station, both run for a good kilometre in a wide arc directly parallel to the Main.

The Kinzig and its floodplain are crossed on bridges made of solid steel girders on brick pillars and abutments built in 1926.

The construction of the North Main S-Bahn is planned along the Frankfurt-Hanau line which will add another two tracks south of the existing ones.