The smallest medieval parish church in Greifswald was first mentioned in a document in 1275. Around 1400 it was converted into a three-aisled hall and the choir was added. During the 30 Years War the church was used as a grain and flour store. The medieval interior was completely destroyed during the Napoleonic occupation of Greifswald from 1807 to 1813. Only the font from the 13th century was preserved. The architect and university teacher Johann Gottfried Quistorp began redesigning the church interior in 1817. After a fire in 1955, a new helmet was put on the tower in 1966. The beautiful painted choir windows and the huge church roof were renovated in 2002 after St. Jacobi had been chosen as the exhibition and event space for the much-noticed North German presentation "Ways of the Brick Gothic". Caspar David Friedrich made numerous pencil drawings and oil paintings such as "Klosterfriedhof im Schnee" (1818/19) or "Miesen vor Greifswald" (1820/22) with the Jacobi Church in focus.
The church is located on the European Route of Brick Gothic, Schwedenstrasse and Caspar-David-Friedrich-Bildweg.