St. Catherine's had an organ as early as the late 15th century, and by the 16th century it was considered the most important in Hamburg. This organ was replaced by a new organ built by Hans Stellwagen, rebuilt in 1670 and repaired by Johann Friederich Besser. In 1720, according to Johann Mattheson, this organ consisted of some 58 stops and approximately 88 ranks—disposed over 4 manuals and pedals—which may have made it the largest organ in the world at that time.
Among the organists who played here were Heinrich Scheidemann, Johann Adam Reinken (organist there for more than 40 years), and Johann Sebastian Bach. Bach first visited the church in the summer of 1701 and played here again in October/November 1720 when he auditioned for the post of organist at the nearby Jacobikirche; his Fantasy and Fugue in G minor, BWV 542 dates to this occasion. Bach greatly admired this organ, which featured two 32-foot ranks in the pedal, with four 16-foot ranks on the Hauptwerk (or Great) division and 16 diagonal shoe bellows to supply the wind to the instrument's windchests. Repairs were made in 1742, and a new lavishly carved decorated case was built; it was adorned with gilding and cherubs along with statues of angels playing trumpets.The organ and its case were destroyed during bombing of Hamburg during the Second World War, though 520 pipes from 20 different stops were preserved. Together with photographs of the case and a pre-1943 description, these pipes form the starting point for a scientific reconstruction of the instrument.