The Dehong region was inhabited long before Emperor Wu (Han Dynasty 156 - 87 BC) decided to pave parts of the Southern Silk Road through the region in 109 BC. The Southern Silk Road was an important trade route through the mountains and valleys of Yunnan, linking Baoshan with Dehong and delving far into Burma, India and other bordering countries. During the Han (206 BC – 220 AD) and Tang Dynasties (618 -907 AD) this line of communication created ties between China and countries in Asia, Africa and Europe. It also played a role in developing the economy and culture of the minority groups on China's southwestern border.

In 1277, Kublai Khan fought a famous battle in Baoshan, the neighboring region to Dehong. With 12,000 Mongol troops, Khan beat out the 60,000 Burmese soldiers and their 2,000 elephants in large-scale warfare against the Burmese king. As the story goes, Khan’s archers were able to start a stampede of the Burmese elephants back against their own lines. Khan then left relatives to govern from within walled towns.

Later, the area was mainly controlled by hereditary land owners. In the 1940s, 250,000 Chinese troops fought to keep the Japanese from invading through Burma. The Japanese Air Force repeatedly bombed the Flying Tigers base not far from Dehong. The Flying Tigers were a volunteer group from the American army who trained in Burma before the Americans joined WWII. They are famous for downing 300 enemy aircrafts with a loss of only twelve of their own in combat.

In most recent times, Dehong has gotten a reputation for the types of wonderful goods that have passed through the border. Yunnan's most western town, Ruili, is one of the first-class national border ports. Some predict the town to become the next big destination in Yunnan for travelers.