At the same time, his cousin, Harsiese became High Priest of Amun at Karnak, perhaps as an appointee of Osorkon II (or his father). However, this was perhaps an unwise move, for it created problems when, in year four of Osorkon II's reign, Harsiese declared himself king in the south. Had Harsiese's father, Shoshenq II  lived, it might have been he who would have inherited the throne in the first place. Yet, Harsiese's declaration held little real power, perhaps because of a continuing illness. In fact, his skull contains a hole, apparently made through a surgical procedure, which Harsiese seems to have survived, to judge from the healing shown by the wound. He was buried in the trough of a granite coffin taken from the tomb of Ramesses II's sister, Henutmire. Nevertheless, while Hariese's claim to the throne may have not provided him with much power, it does seem to have limited the rule of Osorkon II. 

Upon Harsiese's death, Osorkon II consolidated his position by appointing one of his sons, Nimlot C, as High Priest at Karnak. He went on to appoint another son, Sheshonq D, as High Priest of Ptah at Memphis and made his young son (under the age of 10), Harnakhte, High Priest of Amun at Tanis, the royal capital. Obviously, his considerations for this were motivated by politics rather than religiously. In fact, an interesting inscription on a statue from Tanis dated to the reign of Osorkon II petitions Amun to confirm the appointment of his children to various high civil and religious offices. Nimlot C was also governor of Hierakleopolis and Middle Egypt as well as Chief Priest of Arsaphes. 

Osorkon II initiated major building works during his reign, particularly at Babastis in the temple of the tutelary cat-goddess Bastet. He built for himself there a fine, monumental red granite hall to celebrate his jubilee (sed festival) in year 22 of his reign, which he adorned with reliefs of himself and his wife, Karomama I. It is unknown why he deviated from the normal thirty-year threshold for such a festival, but also recorded with these reliefs was the reintroduction of an 18th Dynasty policy of fiscal exemption for the temples of Egypt, which had once been announced by Amenhotep III at Soleb. 

He also built at Memphis, Tanis, Thebes and Leontopolis, which would become the seat of power for the following dynasty of kings. At Tanis, his contributions included a new forecourt where a stelophorous statue of the king was discovered, and other outlying structures to the Temple of Amun. Much of the stone for this work was derived from the demolition of Piramesses, Ramesses II's old capital. 

By the end of his reign, Assyria under king Shalmaneser III (858-828 BC), was wielding considerable influence over the Levant after overcoming northern Mesopotamia and Syria. Hence, in 853, Egypt was forced to confront the threat by aligning with Israel and the neighboring kingdoms, including her old ally Byblos so that together, they could halt the Assyrian advance, which they did at the battle of Qarqar on the Orontes. However, Egypt's involvement in this seems to have been limited to a thousand troops that were contributed to the coalition. During the very last years of Osorkon II's reign, he took an alternative approach to the Assyrian problem, offering gifts of various exotic fauna to the foreign king.

Little else is really known about the final years of this king's reign, the last flourish of the 22nd Dynasty, except that Thebes apparently made another attempt at gaining independence. During the king's last two years, apparently he shared the kingdom with a certain Takelot II of Thebes, effectively marking the end of Egypt as a unified state for a period of nearly two centuries. Even a Biblical passage from this period suggests such a split, when it refers to the "kings of Egypt".

Upon his death, Osorkon II was buried at Tanis in the tomb (NRT 1) he had earlier appropriated for himself and his late father. He was interred in a huge sarcophagus with a lid carved from the remains of a group-statue of the Ramesside Period. He shared the burial chamber with his young son, Harnakhte, who's tenor as High Priest of Amun at Tanis was apparently short-lived.

Unfortunately, his tomb was robbed during antiquity, leaving only a few debris of the hawk-headed coffin and canopic jars behind. He was succeeded by Shoshenq III, who was presumably his son, though no certain evidence survives. 

Granite head of Osorkon II from Tanis

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