Boso's successor Gisilher, a confidant of the new Emperor Otto II, from 971 procured the suppression of the see in favour of his aims to become Archbishop of Magdeburg, finally reached through the Emperor's power over Pope Benedict VII in 981. However this step was clearly against the interests of the Church and the position of Magdeburg archbishopric was decisively enfeebled after the Great Slav Rising of 983, therefore the dissolution was revoked by the papacy in 998 or early in 999 at a Roman synod. Upon Archbishop Gisilher's death in 1004, King Henry II re-established the prince-bishopric; the diocese did not, however, recover all its former territory, and was now almost exclusively a missionary jurisdiction among the Sorbs, who were not fully converted to Christianity until the middle of the 12th century.
Under Bishop Thietmar (1009-1018) the erection of Merseburg Cathedral began, it was consecrated in 1021 in presence of Emperor Henry II. During the Investiture Controversy the Merseburg bishops sided with Pope Gregory VII and also joined the Great Saxon Revolt, which, however, could not stop the dwindling importance of the small diocese. From the 13th century onwards, the bishops had to deal with rising power of the Meissen margraves of the Wettin dynasty, from 1423 Electors of Saxony, who by denying Merseburg's Imperial immediacy attempted to acquire the overlordship. By the 1485 Treaty of Leipzig the Wettins allocated the protectorate over Merseburg to Duke Albert III of Saxony.
The bishopric's fate was sealed with the Protestant Reformation, which was enforced here during the episcopate of Prince Adolph II of Anhalt, who was driven out of office by his uprising subjects during the German Peasants' War in 1525. In 1544 Elector Augustus of Saxony finally assumed the rule as Protestant administrator, with Prince George III of Anhalt as Coadjutor bishop. In 1561 the Saxon elector installed his minor son Alexander as administrator, who nevertheless died four years later, whereafter the Bishopric of Merseburg was finally incorporated by the Saxon electorate. From 1652 to 1738 the descendants of the Wettin duke Christian I held the title of a "Duke of Saxe-Merseburg".
At the 1815 Congress of Vienna, three-fourths of the former diocesan territory was assigned to the Kingdom of Prussia, the rest remaining Saxon; the religious attitude of the people was by that time almost entirely Lutheran.
