In 1763, Chief Seckas of the Thames River brought 170 warriors to the siege of Detroit during Pontiac's uprising. The reserve was established in 1819, as part of a treaty by which the Chippewas of the Thames agreed to share 552,000 acres (2,234 km²) of land with the British for an annuity of £600 and the establishment of two reserves, of which reserve no. 42 is the larger. In 1840 the Chippewas reached an agreement with the Munsee-Delaware Nation to the allow the Munsee to live on 1 square mile near the Thames river. The Munsee portion of the reserve became part of the new Munsee-Delaware Nation No. 1 reserve in 1967.
Chippewas of the Thames First Nation's Chief and Council are elected officials who serve a two (2) year term of office. The current elected officials are Chief R.K. "Joe" Miskokomon, and Councillors G. Clinton Albert, Beverly Deleary, Nancy Deleary, Larry French, H. Rawleigh Grosbeck, Sr., George E. Henry, Myeengun (Arnold "Allan") Henry, Shane Henry, Felicia Huff, Warren Huff, Betsy Kechego and Darlene Whitecalf. Their elected term concludes on 07/27/2015.
In April 2004, the Chippewas of the Thames First Nation had a registered population of 2221, of whom 876 lived on the reserve. By January 2011, the Nation had a total registered population of 2462, of whom 911 lived on the reserve.