The Commerce Clause describes an enumerated power listed in the United States Constitution (Article I, Section 8, Clause 3). The clause states that the United States Congress shall have power "to regulate Commerce with foreign Nations, and among the several States, and with the Indian Tribes". Courts and commentators have tended to discuss each of these three areas of commerce as a separate power granted to Congress. It is common to see the individual components of the Commerce Clause referred to under specific terms: the Foreign Commerce Clause, the Interstate Commerce Clause, and the Indian Commerce Clause.

Dispute exists within the courts as to the range of powers granted to Congress by the Commerce Clause. As noted below, it is often paired with the Necessary and Proper Clause, and the combination used to take a more broad, expansive perspective of these powers.^{[citation needed]}

During the Marshall Court era (1801–1835), interpretation of the Commerce Clause gave Congress jurisdiction over numerous aspects of intrastate and interstate commerce as well as activity that had traditionally been regarded not to be commerce. Starting in 1937, following the end of the Lochner era, the use of the Commerce Clause by Congress to authorize federal control of economic matters became effectively unlimited. The US Supreme Court restricted congressional use of the Commerce Clause somewhat with United States v. Lopez (1995).

The Commerce Clause is the source of federal drug prohibition laws under the Controlled Substances Act. In a 2005 medical marijuana case, Gonzales v. Raich, the U.S. Supreme Court rejected the argument that the ban on growing medical marijuana for personal use exceeded the powers of Congress under the Commerce Clause. Even if no goods were sold or transported across state lines, the Court found that there could be an indirect effect on interstate commerce and relied heavily on a New Deal case, Wickard v. Filburn, which held that the government may regulate personal cultivation and consumption of crops because the aggregate effect of individual consumption could have an indirect effect on interstate commerce.

Article I, Section 8, Clause 3:

[The Congress shall have Power] To regulate Commerce with foreign Nations, and among the several States, and with the Indian Tribes;

The significance of the Commerce Clause is described in the Supreme Court's 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. Then, in response to rapid industrial development and an increasingly interdependent national economy, Congress "ushered in a new era of federal regulation under the commerce power," beginning with the enactment of the Interstate Commerce Act in 1887 and the Sherman Antitrust Act in 1890.