In American political discourse, states' rights are political powers held for the state governments rather than the federal government according to the United States Constitution, reflecting especially the enumerated powers of Congress and the Tenth Amendment. The enumerated powers that are listed in the Constitution include exclusive federal powers, as well as concurrent powers that are shared with the states, and all of those powers are contrasted with the reserved powers—also called states' rights—that only the states possess. Since the 1940s, the term "states' rights" has often been considered a loaded term or dog whistle because of its use in opposition to federally-mandated racial desegregation and, more recently, same-sex marriage and reproductive rights.

The balance of federal powers and those powers held by the states as defined in the Supremacy Clause of the U.S. Constitution was first addressed in the case of McCulloch v. Maryland (1819). The Court's decision by Chief Justice John Marshall asserted that the laws adopted by the federal government, when exercising its constitutional powers, are generally paramount over any conflicting laws adopted by state governments. After McCulloch, the primary legal issues in this area concerned the scope of Congress' constitutional powers, and whether the states possess certain powers to the exclusion of the federal government, even if the Constitution does not explicitly limit them to the states.

The Supremacy Clause of the U.S. Constitution states:

This Constitution, and the Laws of the United States which shall be made in pursuance thereof; and all treaties made, or which shall be made, under the authority of the United States, shall be the supreme law of the land; and the judges in every state shall be bound thereby, anything in the constitution or laws of any state to the contrary notwithstanding. (Emphasis added.)

In The Federalist Papers, ratification proponent Alexander Hamilton explained the limitations this clause placed on the proposed federal government, describing that acts of the federal government were binding on the states and the people therein only if the act was in pursuance of constitutionally granted powers, and juxtaposing acts which exceeded those bounds as "void and of no force":

But it will not follow from this doctrine that acts of the large society which are not pursuant to its constitutional powers, but which are invasions of the residuary authorities of the smaller societies, will become the supreme law of the land. These will be merely acts of usurpation, and will deserve to be treated as such.^{[citation needed]}

In the period between the American Revolution and the ratification of the United States Constitution, the states had united under a much weaker federal government and a much stronger state and local government, pursuant to the Articles of Confederation. The Articles gave the central government very little, if any, authority to overrule individual state actions. The Constitution subsequently strengthened the central government, authorizing it to exercise powers deemed necessary to exercise its authority, with an ambiguous boundary between the two co-existing levels of government. In the event of any conflict between state and federal law, the Constitution resolved the conflict via the Supremacy Clause of Article VI in favor of the federal government, which declares federal law the "supreme Law of the Land" and provides that "the Judges in every State shall be bound thereby, any Thing in the Constitution or Laws of any State to the Contrary notwithstanding." However, the Supremacy Clause only applies if the federal government is acting in pursuit of its constitutionally authorized powers, as noted by the phrase "in pursuance thereof" in the actual text of the Supremacy Clause itself (see above).

When the Federalists passed the Alien and Sedition Acts in 1798, Thomas Jefferson and James Madison secretly wrote the Kentucky and Virginia Resolutions, which provide a classic statement in support of states' rights and called on state legislatures to nullify unconstitutional federal laws. (The other states, however, did not follow suit and several rejected the notion that states could nullify federal law.) According to this theory, the federal union is a voluntary association of states, and if the central government goes too far each state has the right to nullify that law. As Jefferson said in the Kentucky Resolutions: