The first known city built at the site of Guangzhou was Panyu founded in 214 BC. The city has been continuously occupied since that time. Panyu was expanded when it became the capital of the Nanyue Kingdom in 206 BC.

The Han Dynasty annexed Nanyue in 111 BC, and Panyu became a provincial capital and remains so today. In 226 AD, the city however became the seat of the Guang Prefecture. Therefore, "Guangzhou" was the name of the prefecture, not of the city. However, people grew accustomed to calling the city Guangzhou, instead of Panyu.

The city has always be an important port city for the Middle Kingdom for centuries, until Qing Dynasty - Guangzhou quickly emerged as one of the most suitable ports for international trade and before long ships arrived from all over the world.

The Portuguese in Macau, the Spanish in Manila, Armenians, and Muslims from India were already actively trading in the port by the 1690s, when the French and English began frequenting the port through the Canton System.

Other companies were soon to follow: the Ostend General India company in 1717; Dutch East India Company in 1729; the first Danish ship in 1731, which was followed by a Danish Asiatic Company ship in 1734; the Swedish East India Company in 1732; followed by an occasional Prussian and Trieste Company ship; the Americans in 1784; and the first ships from Australia in 1788.

By the middle of the 18th century, Guangzhou had emerged as one of the world's great trading ports under the Thirteen Factories, which was a distinction it maintained until the outbreak of the Opium Wars in 1839 and the opening of other ports in China in 1842. The privilege during this period made Guangzhou one of the top 3 cities in the world.

After 1980s, Guangzhou led the entire country to be 1 of the earliest cities that were open to the world which also led to its rapid economic growth due to the city's close proximity to Hong Kong and access to the Pearl River.

As labor costs increased in Hong Kong, manufacturers opened new plants in the cities of Guangdong including Guangzhou. As the largest city in one of China's wealthiest provinces, Guangzhou attracts farmers from the countryside looking for factory work hence its large labor force. Over 20 countries have setup their Consulate Generals in Guangzhou, including the United States.

Guangzhou will continue to the lead the country in economy growth, as it has done for centuries.