Zhu Ran was born in 182 AD in Danyang, Yang Province, in southern China. He studied alongside Sun Quan, and at the age of thirteen, he was adopted by his uncle Zhu Zhi, who was a strategist under Sun Jian, Sun Quan's father. When Sun Quan became the new head of the House of Sun in 200 AD, Zhu Ran was given command of 2,000 troops and put down mountain bandits, and he raced time to build fortifications to resist Cao Cao's invasion at the Second Battle of Ruxukou. In 219 AD he also took part in Lu Meng's invasion of Jing Province and captured Guan Yu in Linju after the Battle of Fan Castle.
When Lu Meng was dying, he recommended Zhu Ran as commander after his death, and Sun Quan appointed him as Governor of Jiangling. In 222 AD, he served under Lu Xun at the Battle of Xiaoting, where he commanded Wu's naval forces. He crushed the invading Shu army's spearhead, pursued the retreating army, and cut down their supply lines. Zhu Ran is credited as the mastermind of the fire attack that led to the rout of Shu ruler Liu Bei's forces, although it was really executed by Han Dang. In Luo Guangzhong's fictional account of the "Battle of Yiling" in the Romance of the Three Kingdoms, Zhu Ran was killed by Shu commander Zhao Yun while he was pursuing Liu Bei, allowing Liu Bei to escape to Baidi Castle. In 223 AD, a year later, he defended Jiangling from a Wei invasion led by Cao Zhen, Xiahou Shang, and Zhang He, and he killed defecting officer Yao Tai. After months of siege without reinforcements from Sun Sheng, Pan Zhang, or Yang Yue, it appeared to Wei that Jiangling would soon fall. However, the city held firm, and Emperor Cao Pi's army was forced to withdraw.
In 229 AD, Zhu Ran was declared the Governor of Piaoji, and with 800 men, he fought off Wei invaders under Pu Zhong and Hu Zhi when they attacked Lu Xun's army. After Lu Xun died in 245 AD, Zhu Ran became a politician, and along with Zhuge Ke and Bu Xie, he ran the Wu court. When he was ill in his last years, Sun Quan lost lots of pounds from worry and loss of sleep, and he died in 249. His funeral was the third-largest in the history of Wu after Lu Meng and Ling Tong.