Guangzhou is an ancient city. As early as 5000 BC, there were Neolithic sites in the area, and in the eighth century BC, migrants from the Yangtze River valley brought settled agriculture to the region. The city of Guangzhou proper dates back 2200 years. In 214 BC, the founder of the Qin Dynasty unified China, establishing Nanhai Prefecture with the city of Guangzhou as its walled seat. Far from the constant warfare of Northern China, Guangzhou attracted migrants and grew economically into China's unrivalled southern metropolis.

During the Han dynasty, Guangzhou developed into an important regional market centre and foreign trade port. It became the chief port on the "Silk Road of the Sea", trading silk, porcelain, and tea to Arab, Indian, and Southeast Asian merchants. During the Tang and Song Dynasties, the imperial court's official policy of promoting maritime trade allowed Guangzhou to further develop its foreign connections. At this time, Guangzhou had a resident foreign population of approximately 10,000. During the Song Dynasty, road improvement also allowed greater access to China's interior.

In the late Song and Ming Dynasties, foreign trade declined due to upheaval in the Arab world and the rise of ports in neighboring Fujian Province,but with the establishment of Macau as a Portuguese colony in the 16th century, Guangzhou's situation once again improved. European traders in Southern China were restricted to Guangzhou, giving the city a virtual monopoly over foreign trade. However, economic relations with the outside world created tensions on both sides, culminating in the Anglo-Chinese Opium Wars. After a devastating loss to the British, China was forced to open up five treaty ports for foreign trade, including Guangzhou, and relinquish control over Hong Kong, resulting in more overt foreign influences.

Guangzhou continued to grow in the early 20th century and built an industrial base to supplement its trading function. In the 1920s and 1930s, the completion of the Guangzhou-Sanshui, Guangzhou-Kowloon, and Beijing-Guangzhou railways, as well as improved water transportation, reinforced Guangzhou's central position in Southern China. However, as the capital of Guangdong Province, a strategically vulnerable province near China's sensitive border with Vietnam, Guangzhou suffered neglect by the central government during the Maoist period.

With the ending of the Vietnam conflict and the rising prosperity of Southeast Asia, Guangzhou once again became a prominent target of economic growth. As one of China's first "open cities" under the post-Mao economic reforms, Guangzhou grew significantly, attracted Foreign Direct Investment, and developed a stronger industrial base.