The official history of the Osthofen concentration camp begins with a decree by the State Commissar for the Police in Hesse, Werner Best, on 1 May 1933.

After the 28 February 1933 Reichstag Fire Decree, civil liberties in Germany became restricted, and large numbers of Communists were arrested.

[1] Karl d'Angelo [de; fr], a SS Sturmbannführer and the local Osthofen Nazi Party chairman, was made honorary camp leader on orders of Werner Best.

[2] Camp doctor was Reinhold Daum [de], who declared every single new arrival healthy and medically fit for imprisonment even if they had been mistreated.

[1] Despite the poor living conditions and hygiene in the camp, with prisoners originally sleeping on the concrete floor, there are no recorded inmate deaths at Osthofen.

[12] In a nearby "Camp II", which was used for aggravated detention, prisoners had to spend the nights in wire cages, with lights on that made sleep difficult.

[3] Former prisoners, supported by the Union of Persecutees of the Nazi Regime, started efforts to commemorate the history in 1972, which was at the time opposed by locals.

[7] After further activist involvement by the youth wing of the German Trade Union Confederation and others, the camp building became a protected monument in 1989.

[7] In her 1942 novel The Seventh Cross (adapted as a film in 1944), Anna Seghers describes a fictitious "Westhofen" concentration camp located in the same area, clearly referring to Osthofen.

[7] While The Seventh Cross has been called a "memorial" to the Osthofen inmates,[4] its plot, set in 1937, is inspired by an escape from Sachsenhausen concentration camp.