Initial efforts to present a historical and statistical description of the Church of the Holy Roman Empire date from the 16th century. The humanist Kaspar Bruschius’ (1518–1557) developed a paradigm for describing monasteries, the Chronologia monasteriorum Germaniae praecipuorum ac maxime illustrium (Ingolstadt 1551). The Chronologia covers the history of 145 mainly Southern German convents, and documents them alphabetically in the consistent pattern: foundation – endowments – list of abbots.

A first approach of describing dioceses constitute the Epitome de omnibus Germaniae episcopatibus, of which only one volume had been completed (Nürnberg 1549).

The term "Germania sacra" was first used by Gabriel Bucelinus in his Germania topo-chrono-stemmato-graphica sacra et profana (4 volumes, Augsburg 1655–1678). Abbot Martin Gerbert of the St. Blasius convent, located in the Black Forest, was the first to pursue the plan to describe dioceses of the Holy Roman Empire as a joint project. Until 1803, however, only four volumes had been published.

In 1917, Paul Fridolin Kehr (1860–1944), one of the leading German researchers of the Middle Ages, founded the Germania Sacra project (later called "Alte Folge") at the Kaiser-Wilhelm-Institut für deutsche Geschichte in Berlin. Kehr established the Germania Sacra in an effort to connect the approach of regional history to other projects in the field of ecclesiastical history (Germania Pontifica, Repertorium Germanicum), he had founded in Berlin. Those projects were established at the Preußisches Historisches Institut in Rome and at the Vatican Secret Archives.

In 1956 the Germania Sacra was transferred to the newly founded Max-Planck-Institute for History in Göttingen. The directors Hermann Heimpel, Josef Fleckenstein and Otto Gerhard Oexle had published the reference books of the Germania Sacra as “Neue Folge”.

After the closure of the Max-Planck-Institute for History on 31 December 2007, the Germania Sacra has been one of the projects belonging to the Union der deutschen Akademien der Wissenschaften in Germany from 1 January 2008 onwards, limited to a 25 years term. The editorial office is situated at the Akademie der Wissenschaften zu Göttingen and due to the relocation of the project new volumes will be published as “Dritte Folge”.