Zhou Yu hailed from Shuxian (modern Lujiang, Anhui) and had a close friendship with Sun Ce from the beginning. Their wives were sisters. After a short period of service to the warlord Yuan Shu 袁朮, he entered the service of his friend Sun Ce. He occupied the post of Leader of the court gentlemen establishing authority (jianwei zhonglangjiang 建威中郎將) and was made governor (taishou 太守) of the commandery of Jiangxia 江夏 after the conquest of the province of Jingzhou 荊州.
Zhou Yu incited in Sun Ce the idea to create a own, independent empire in southern China. After the untimely death of Sun Ce by murder, Zhou Yu and Zhang Zhao 張昭 took over the command of the troops that were now to serve Sun Ce's younger brother Sun Quan. Zhou Yu suggested erecting a strong city on the east banks of the Yangtze River, a city that was to become the modern Nanjing.
After Cao Cao 曹操 had defeated Yuan Shao 袁紹 at the battle of Guandu 官渡 in 200 and had become the strong man in the north, Zhou Yu also impeded Sun Quan to meet the demands of Cao Cao to send his son as a hostage to the court of Cao Cao.
In 208, Liu Cong 劉琮, who governed Jingzhou, submitted to Cao Cao who advanced a large army towards the middle Yangtze area. While most of Sun Quan's advisors pledged for a submission to Cao Cao, Zhou Yu advocated a war of resistance. Zhou Yu had clearly analysed the advantages of Sun Quan's troops and his territory, as well as Cao Cao's shortcomings. Together with Lu Su 魯肅 and Cheng Pu 程普, he suggested facing the challenge of resisting Cao Cao's army.
A very important strategy was to force an alliance with Liu Bei 劉備, who controlled the region of Shu 蜀 (modern Sichuan). During the battle, the army of Cao Cao was already in a very desparate state because of a plague roaming the camps. General Huang Gai 黃蓋 realized the plan to lit fire to the camp of Cao Cao by sending burning ships river down. The invader withdrew, and Zhou Yu was awarded the title of Determined general (pian jiangjun 爲偏將軍) and appointed governor of Nanjun 南郡. The great success caused Zhou Yu to great plans for the reunification of China, first by conquering Shu from the hands of Liu Zhang 劉璋, then the liberation of the region of Hanzhong 漢中 from the Daoist state of Zhang Lu 張魯, and the final blow to Cao Cao's power in the north. Before all these projects could be started, Zhou Yu died.