The Shang Dynasty established Aodu (隞都) or Bodu (亳都) in Zhengzhou (see also: History of China). This pre-historical city had been long lost even before the time of the First Emperor of China. Since 1950 archaeological finds in a walled city in Eastern Zhengzhou known have provided evidence of Neolithic Shang Dynasty settlements in the area. Outside this city, in addition to remains of large public buildings, a complex of small settlements has been discovered. The site is generally identified with the Shang capital of Ao. It is preserved in the Shang Dynasty Ruins monument in Guanchen District. 

The Shang, who continually moved their capital due to frequent natural disasters, left Ao at around 13th century BC. The site, nevertheless, remained occupied; Zhou (post-1050 BC) tombs have also been discovered. Traditionally it is held that in the Western Zhou period (1111–771 BC) it became the fief of a family named Guan. From this derives the name borne by the county (xian) since the late 6th century BC — Guancheng (City of the Guan). The city first became the seat of a prefectural administration in AD 587, when it was named Guanzhou. In 605 it was first called Zhengzhou — a name by which it has been known virtually ever since.

The name Zhengzhou came from the Sui Dynasty (AD 581), even though it was located in Chenggao, another town. The government moved to the contemporary city during the Tang Dynasty. It achieved its greatest importance under the Sui (AD 581–618), Tang (618–907), and early Song (960–1127) dynasties, when it was the terminus of the New Bian Canal, which joined the Yellow River to the northwest. There, at a place called Heyin, a vast granary complex was established to supply the capitals at Luoyang and Chang'an to the west and the frontier armies to the north. In the Song period, however, the transfer of the capital eastward to Kaifeng robbed Zhengzhou of much of its importance. It was a capital during the five dynasties of Xia, Shang, Guan, Zheng, and Han, and a prefecture during the eight dynasties of Sui, Tang, Five Dynasties, Song, Jin, Yuan, Ming, and Qing.

In 1903 the Beijing–Hankou railway arrived at Zhengzhou, and in 1909 the first stage of the Longhai Railway gave it an east–west link to Kaifeng and Luoyang; it later was extended eastward to the coast at Lianyungang, Jiangsu Province, and westward to Xi'an (Chang'an), Shaanxi Province, as well as to western Shaanxi. Zhengzhou thus became a major rail junction and a regional center for cotton, grain, peanuts, and other agricultural produce. Early in 1923 a workers' strike began in Zhengzhou and spread along the rail line before it was suppressed; a 14-story double tower in the center of the city commemorates the strike. In 1938, during the war with Japan, the retreating Chinese Nationalist Army blew up the dikes retaining the Yellow River about 32 km northeast of the town, flooding a vast area. At about the same time, in their drive to relocate industry in the interior far from the invading Japanese, the Chinese transferred all the local plants to the west.

When the Communist government came to power in 1949, Zhengzhou was a commercial and administrative center, but it had virtually no industry. Because it was the center of a densely populated cotton-growing district, it was developed into an industrial city, with industry concentrated on the west side so that the prevailing northeast winds would blow fumes away from the city. There are cotton-textile plants, spinning mills, textile-machinery works, flour mills, tobacco and cigarette factories, and various food processing plants; coal is mined nearby.

Zhengzhou also has a locomotive and rolling-stock repair plant, a tractor-assembly plant, and a thermal generating station. The city's industrial growth has resulted in a large increase in the population, coming predominantly from industrial workers from the north. Trees have been planted throughout the city's more than 23 km² area, holding down the sand that formerly blew in thick gusts through the city. A water diversion project and pumping station, built in 1972, has provided irrigation for the surrounding countryside. The city has an agricultural university.