Tillamook Bay, which encompasses a 597-square-mile watershed, is the largest of the five bays in Tillamook County. The bay is fed by five principal rivers: the Wilson, Trask, Miami, Tillamook, and Kilchis. It supports a strong oyster industry and provides excellent salmon fishing and commercial crabbing. Sport and charter fishing contribute significantly to the local economy.

The bay has a rich cultural history. Two prominent Native American sites at Kilchis Point and Goose Point have been dated to the fifteenth century, and cultural resource assessments continue in this area. Archaeological evidence places human occupation of the area to at least 11,500 BP; attempts to document the area more thoroughly have been hindered by the erosion of the coastline.

The Salish-speaking Tillamook people, or Killamook, traded regularly with other neighboring tribal communities along the Oregon Coast, including the Nestucca, Nehalem, and Clatsop. In 1805-1806, Lewis and Clark cited an interest in acquiring the high-quality canoes built by the Tillamook. The Tillamook are perhaps best known for their extraordinary basket-weaving skills.

Captain Robert Gray, sailing the Lady Washington, came ashore in August 1788 for supplies, making him and his crew the earliest recorded U.S. citizens to visit Tillamook Bay. A skirmish with the local inhabitants left Gray's Black servant, Marcos Lopez, dead, and Gray dubbed the place Murderer’s Harbor. 

The first white settler, Joe Champion, moved to the area in 1851. By 1900, the communities of Bay City, Garibaldi, Hobsonville, and Barview were established on the east shore of Tillamook Bay, and the City of Tillamook and community of Idaville were established along the rivers and sloughs draining into the bay.

Until development of railroad lines in the county in 1911, Tillamook Bay was the principal travel and supply route. The federal government dredged the Houquarton Slough to ensure that large ships could supply Tillamook residents. In the late nineteenth century, the Army Corps of Engineers designed and installed dikes in Tillamook Bay to create a navigable channel from the town of Tillamook and the Houquarton Slough to the mouth of Tillamook Bay in Barview. The dikes determine the principal navigation paths and salmon runs for the entire bay.

In the early 1900s, a planned community called Bayocean was established on Bayocean Spit, the four-mile western border of Tillamook Bay, from Cape Meares in the south to the jetty at Barview in the north. Bayocean achieved some prominence until the construction of the north jetty at the mouth of Tillamook Bay. It would be forty years before the south jetty was constructed. During that time, Bayocean collapsed into the Pacific, and Bayocean Spit is now uninhabited.

Today, Tillamook Bay is principally a recreation area that attracts fishers and tourists to kayaking and water trails. The Tillamook Estuary Partnership and its partners provide a strong preservation effort, including current efforts to restore the Miami River estuary to its natural course.