The first section of the line between Bützow and Güstrow was opened in 1850 by the Mecklenburg Railway Company (German: Mecklenburgische Eisenbahngesellschaft) and is one of the oldest railways in Germany and is part of the Leipzig–Magdeburg–Schwerin–Rostock main line.

As there were few wealthy investors, the Güstrow–Neubrandenburg line was built by the government of Mecklenburg-Schwerin at the initiative of Grand Duke Frederick Francis (Friedrich-Franz) II.

Strasburg was on the border of lines controlled by railway divisions in Schwerin and Stettin.

A continuous D-express and an ordinary express ran to Hamburg, and four pairs of ordinary trains ran to Stettin (and five between Bützow and Güstrow), with one of them also running all the way from Hamburg to Stettin.

The section from the border at Grambow to Szczecin became part of Polish State Railways (PKP).

The second track, which existed west of Teterow, was dismantled after the war, making it a single-track line, as it still is.

Because of the dismantling of the Lloyd Railway between Neustrelitz and Plaaz for reparations to the Soviet Union trains between Berlin and Rostock ran from 1945 to 1961 via Güstrow and Neubrandenburg.

Passenger services were only resumed in May 1972, following the introduction of visa-free travel between East Germany and Poland.

As a result, three to four pairs of trains ran to Szczecin, the rest ended in Grambow.

In 1995 Regional-Express trains (stopping in Güstrow, Teterow, Malchin, Stavenhagen, Neubrandenburg and Strasburg) ran approximately every two-hour and took about 130 minutes to run and were followed by Regionalbahn trains, stopping at all stations.