The Commerce Clause is an enumerated power listed in the United States Constitution. It is found in Article 1, Section 8, Clause 3 of the Constitution, which gives Congress the power "to regulate Commerce with foreign Nations, and among the several States, and with the Indian Tribes". The Commerce Clause has been the most broadly-interpreted clause in the Constitution, making way for many laws that some argue contradict the original intended meaning of the clause.

The significance of the Commerce Clause is described in the Supreme Courts opinion in Gonzales v. Raich, 545 U.S. 1 (2005): "The Commerce Clause emerged as the Framers response to the central problem giving rise to the Constitution itself: the absence of any federal commerce power under the Articles of Confederation. For the first century of our history, the primary use of the Clause was to preclude the kind of discriminatory state legislation that had once been permissible".

The Commerce Clause has been used by Congress to justify exercising legislative power over the activities of states and their citizens, leading to significant and ongoing controversy regarding the balance of power between the federal government and the states. Courts have generally taken a broad interpretation of the Commerce Clause for much of United States history. However, there have been periods where the Supreme Court has narrowed its interpretation of the clause, such as during the Lochner era from 1905 to 1937.

The Commerce Clause has been interpreted both as a grant of positive authority to Congress and as an implied prohibition of state laws and regulations that interfere with or discriminate against interstate commerce. The latter interpretation, of implied prohibition, is the so-called “dormant” commerce clause. In its positive interpretation, the Commerce Clause serves as the legal foundation of much of the government’s regulatory power.

The Commerce Clause is an important source of those powers delegated to Congress and its interpretation is very important in determining the scope of federal power in controlling innumerable aspects of American life.