Chippewa of the Thames First Nation No. 42 is an Indian reserve on the Thames River 24 km west of St. Thomas, Ontario, Canada. Its area is 33.3 km². In April 2004 the Chippewa of the Thames First Nation had a registered population of 2,221, of whom 876 lived on the reserve.

In 1796, Chief Seckas of the Thames River brought 170 warriors to the seige of Detroit during Pontiac's uprising. The reserve was established in 1819, as part of a treaty by which the Chippewa of the Thames sold 552,000 acres (2,234 km²) of land to the British for an annuity of £600 and the establishment of two reserves, of which reserve no. 42 is the larger. In 1840 the Chippewa reached an agreement with the Munsee-Delaware Nation to share the reserve. The Munsee portion of the reserve became part of the new Munsee_Delaware Nation No. 1 reserve in 1967.