The USITC is responsible for conducting global safeguard (escape clause) and market disruption investigations under the Trade Act of 1974. Under the U.S. global safeguard law (section 201 of the Trade Act of 1974), if the USITC determines that an article is being imported into the United States in such increased quantities as to be a substantial cause of serious injury or threat of serious injury to a domestic industry producing a like or directly competitive product, it recommends to the President relief that would remedy the injury and facilitate industry adjustment to import competition. The President makes the final decision concerning whether to provide relief and the type and duration of relief. Relief is temporary and for the purpose of providing time for the industry to adjust to import competition. Relief may take the form of increased tariffs, tariff-rate quotas, quotas, adjustment measures (including trade adjustment assistance), and negotiation of agreements with foreign countries. In making its determination, the USITC is not required to find an unfair trade practice.

In China safeguard investigations under section 421 of the Trade Act of 1974, the USITC determines whether a product from China is being imported into the United States in such increased quantities or under such conditions as to cause or threaten to cause market disruption to the domestic producers of like or directly competitive products. If the USITC makes an affirmative determination, it proposes a remedy. The Commission sends its report to the President and the U.S. Trade Representative. The President makes the final remedy decision.

The USITC also conducts country or region-specific safeguard investigations under U.S. legislation that implements U.S. free trade agreements, including agreements with Canada and Mexico (NAFTA), and Singapore . If the USITC finds, as a result of a duty reduction under an agreement, that a domestic industry is seriously injured or threatened with serious injury by increased imports, it recommends a form of relief to the President. The President makes the final decision on relief. The relief is temporary and may be in the form of a rollback of a duty reduction under the agreement or suspension of further duty reductions on the imported good.