Ezhou has a long and storied history dating back to the Three Kingdoms period. In 221 AD, Sun Quan moved his capital to E County and renamed it Wuchang, making it one of the key political centers of the Eastern Wu Kingdom. The poet Su Dongpo's famous "Ode to the Red Cliff" mentions this region.
During the Ming and Qing dynasties, Ezhou was an important river port and trading center along the Yangtze River. The city's fortunes declined somewhat in the 20th century when Wuhan grew to dominate the region, but Ezhou retained its importance as a fishing and agricultural center.
The city's administrative status was upgraded from county to prefecture-level city in 1983. Since then, it has developed steadily, focusing on manufacturing, logistics, and eco-tourism centered on Liangzi Lake.