The native Duwamish people inhabited the area that is now Tukwila for thousands of years. According to native mythology, the site formed when a spirit Muskrat brought up the first bit of earth from the river so the tribes could have a place to "make the four divisions of the world." (Reinart, 1991). Although Spanish and English explorers first came to the area in the 1830s, they did not establish homesteads until the mid-1850s. Many of the newcomers were northern Europeans, including Swedes and Germans. As they cleared the land for farming, the Duwamish were displaced. Today few Native Americans remain in Tukwila, although the Muckleshoot Reservation is nearby to the north.

In the early days of settlement, the river system served as the primary transportation system throughout the region. Three rivers ran through the valley: the Duwamish and Green Rivers oriented north/south, and the Black River oriented east/west, emptying into the Green River. Over time, much of the river system has been diverted, dammed, and channeled to allow for residential and industrial development both in Tukwila and in the Seattle metropolitan region.

But transportation continued to be a key factor in the development of Tukwila. The Interurban Railway operated between 1902 and 1928, providing an efficient method for commuters to travel between Tukwila and Seattle. New road technologies (such as the use of new paving materials) were tested in Tukwila. As the automobile became more popular and usable due to new roads (such as Pacific Highway), the railway system declined.

The city of Tukwila incorporated in 1908. The name "Tukwila" is believed to be a native Duwamish phrase meaning "land where the hazelnuts grow." First used for one of the Interurban stations in the Duwamish valley, the name took hold. Today, the city's seal is emblazoned with the image of hazelnut flowers.

In the 1950s, the small community of Tukwila and its surrounding neighborhoods joined together to fight back a threat from the Seattle Port Authority. The port intended to deepen the Duwamish at the north end to make it amenable to heavy industrial development, a proposal supported by the Seattle business community, the Seattle City Council, the State Legislature, and many other powerful agents. Feeling that their way of life was in danger, the citizens of Tukwila successfully organized, annexing the surrounding neighborhoods and taking control of land use regulation in these previously unincorporated areas. Through this strategy, the Port Authority's intentions were blocked.