According to the Palermo Stone, Ninetjer, the 3rd king of the 2nd Dynasty, ruled for at least 26 years and there was a military expedition during his 13th year. Like Hotepsekhemwi, Ninetjer too was buried in a tomb at Saqqara.
With the 4th king of this dynasty, Egypt was torn apart by political and religious conflicts. He ascended to the throne using the name Horus-Sekhemib, but somewhere during his reign, he changed his name to Seth-Peribsen. He thus became the only Egyptian king known to have used a Seth-name in stead of a Horus-name. This name changing is highly significant, for in the Egyptian mythology, Horus and Seth were adversaries. It is not known, however, if this part of mythology had already been established during the 2nd Dynasty, which would indicate that Sekhemib at one time wished to break with Egyptian traditions, or whether it has been a result of the conflict that appears to have arisen between Seth-Peribsen and Horus-Khasekhem. If the latter be the case, one might even speculate that Sekhemib/Peribsen could have been Khasekhem’s uncle who ascended the throne illegitimately and that his position was attacked by his nephew. This may have plunged the country into chaos, which might explain the chaotic character that is usually ascribed to Seth. The fact that Horus is usually considered an Upper-Egyptian and Seth a Lower-Egyptian god, even suggests that during at least parts of the reigns of Sekhemib/Peribsen and Khasekhem, the country may have been divided. The struggle between Seth-Peribsen and Horus-Khasekhem was eventually lost by Peribsen, as in mythology. As a sign that the troubles had come to an end, Khasekhem changed his name to Horus-Seth-Khasekhemwi, meaning "Horus-Seth, the two powers have appeared". With the unity of Egypt again firmly re-established, the 2nd Dynasty had come to its end.
The king-lists and Manetho add several other kings to this dynasty, such as Wadjnes and Sened, but they are not attested by contemporary sources.