Clackamas County was named after the Clackamas Indians. The city was built on a portion of Dr. John McLoughlin's land claim and therefore their county seat became Oregon City. In July 5, 1843 Clackamas County was one of the four original districts created by the Provisional Legislature. In 1843 Clackamas County covered portions of four present-day states and one Canadian province. The Columbia River was made the northern boundary of the county in 1844. The United States-Great Britain Boundary Treaty of 1846 relocated the northern border of both the United States and Clackamas County at latitude 49deg. The Act of Congress that created Washington Territory in 1853 enclosed Clackamas County within the present-day boundaries of Oregon. Clackamas County acquired its current boundaries in 1854. The county is bounded by Multnomah County to the north, Wasco County to the east, Marion County to the south, and Yamhill and Washington Counties to the west.

Thousands of immigrants migrated to Oregon City and Clackamas County during the 1840s due to The Barlow Road. From 1842 Oregon City rapidly became the primary urban center in Clackamas County and dominated social and political life in Oregon during the provisional government period. Today, Clackamas County is home to the traditional End of the Oregon Trail and the county's geographical features include numerous rivers - the Willamette, Clackamas, Sandy, Pudding, Molalla, and Salmon, and Mt. Hood. Since its creation, agriculture, timber, manufacturing, and commerce have been the county's principal activities. The population of Clackamas County has steadily increased from 1850 through 1997. The 2000 population of 338,391 represented a 21.35% increase over 1990.