It is believed that the Manobos, Mandayas, Kalagans, Mansakas, and Bagobos occupied the area.

The Davao Region was once part of Sultanate of Maguindanao and was called "Pinagurasan" by the Maguindanaons.

Datu Bago was one of the Datus in Davao Gulf who resisted the Spanish Empire colonization on the region.

In 1512, Francisco Serrano was shipwrecked in the shallow waters and coral reefs of Cape of San Agustín, located in what is now the province of Davao Oriental.

In 1538, Francisco de Castro, a Portuguese ship captain, was driven by strong winds to the southeastern coast of Mindanao.

At that time, the Kalagan Moro chieftain Datu Bago was in control of the area in what is now Davao City.

This is the time the town of Davao, then called Nueva Vergara by the Spaniards, was established in the year 1848.

Although the Spanish gained the upper hand when they finally controlled the ports of the region, the population of Davao grew very slowly until the arrival of Christian missionaries in the area in 1890.

Unlike the major parts of Luzon, Visayas and other coastal parts of Mindanao, Spanish rule in Davao lasted only for 50 years, abandoning it in 1898 when the Philippines became independent from Spain, making it among the shortest-lived areas controlled by Spain.

[5][6] The Moros were judged as "fully capable of dealing with Japanese fifth columnists and invaders alike.

[22] Surigao del Sur was moved to the newly created region Caraga on February 23, 1995.

Filipino and English are also spoken and widely used in schools, businesses, commerce, and industry.

Chinese immigrants are widespread in the region, with a considerable population based in Davao City.

A considerable population of Japanese are also found in the region, most of them also located in Davao City.

Due to the region's rise as the main commercial and industrial hub of Mindanao, many of its workers are oriented to urban services such as putting small-scale businesses and working in commercial industries in thriving urban areas like Davao, Tagum, and Digos.

Both private and foreign investors and businessmen are putting up huge business centers in the region, fueling up its commercial growth rate.

The region has adequate communications facilities, reliable power, and an abundant water supply.

In December 2016, President Duterte helped enter a contract with Chinese investors to create a new port in the region of Isla Verde in Davao.

[39] This involves the creation of three artificial islands by a set of Chinese companies including CCCC Dredging Group Co. Ltd for $200 million.