In the south, Sun Ce, then an independent general under the service of Yuan Shu, defeated the warlords of Yang Province, including Liu Yao,Wang Lang, and Yan Baihu. In 197, Yuan Shu, who was at odds with Cao Cao, Yuan Shao, and Liu Bei, felt assured of victory with his subordinate's conquests, and thus declared himself emperor of the Cheng Dynasty. The move, however, was a strategic blunder, as it drew the ire of many warlords across the land, including Yuan Shu's own subordinate Sun Ce, who had advised Yuan Shu not to make such a move. Cao Cao issued orders to Sun Ce to attack Yuan Shu. Sun Ce complied, but first convinced Cao Cao to form a coalition against Yuan Shu, of which Liu Bei and Lü Bu were members. Attacked on all sides, Yuan Shu was defeated and fled into hiding.

Afterwards, Lü Bu betrayed Liu Bei and seized Xu Province, forming an alliance with Yuan Shu's remnant forces. Liu Bei, together with his followers Zhang Fei and Guan Yu, fled to Cao Cao, who accepted him. Soon, preparations were made for an attack on Lü Bu, and the combined forces of Cao Cao and Liu Bei invaded Xu Province. Lü Bu's men deserted him, Yuan Shu's forces never arrived as reinforcements, and he was bound by his own subordinates Song Xian and Wei Xu and executed on Cao Cao's order.

In 200, Dong Cheng, an imperial relative, received a secret edict from Emperor Xian to assassinate Cao Cao. He collaborated with Liu Bei on this effort, but Cao Cao soon found out about the plot and had Dong Cheng and his conspirators executed, with only Liu Bei surviving and fleeing to join Yuan Shao in the north.