In 2006, in the first federal challenge ever argued against the NSA's warrantless wiretapping program, the ACLU defeated the Bush administration when a district court declared the program unconstitutional. But in July 2007, the 6th Circuit overturned that decision. The ACLU asked the Supreme Court of the United States to consider the ruling, but in February 2008, the Court declined to review the challenge.

The ACLU of Southern California and the ACLU, along with the Jones Day and Stacy Tolchin law firms, filed a lawsuit in July 2014 challenging a federal government program used to deny or delay thousands of law-abiding people - many of them from Muslim-majority countries - citizenship, green cards, and visas on counterterrorism grounds. The program is illegal and unconstitutional, was adopted without any congressional approval or public comment, and violates the Fifth Amendment’s guarantee of due process, as the aspiring Americans whose applications are denied under the program are not told why or given a meaningful opportunity to clear their names. In response to the lawsuit, the government promptly acted upon the applications of all of the plaintiffs, approving three of them, and the case was resolved.

The ACLU of California, the ACLU, Asian Americans Advancing Justice - Asian Law Caucus, and the law firm Bingham McCutchen have filed a lawsuit challenging the federal government's Suspicious Activity Reporting program — a vast expansion of the federal government's domestic intelligence network. The SAR program supposedly facilitates the collection and sharing of information about activity that appears "suspicious," but in practice it targets First Amendment-protected activity, encourages racial and religious profiling, and violates federal law. The plaintiffs are five U.S. citizens whose information has been entered into counterterrorism databases for engaging in lawful conduct, and who have been subject to unwarranted law enforcement and scrutiny. The lawsuit was filed in July 2014 in the U.S. District Court for the Northern District of California. In March 2017, the District Court granted the government’s motion for summary judgment, upholding the SAR program’s standard for data collection. We are appealing that ruling to the Ninth Circuit Court of Appeals.

The American Civil Liberties Union and the Center for Constitutional Rights (CCR) filed a lawsuit in 2012 challenging the government’s targeted killing of three U.S. citizens in drone strikes far from any armed conflict zone. Oral argument was held in July 2013 in Washington, and the court dismissed the case in April 2014.

Government documents obtained by the ACLU show that nationwide programs that collect so-called "Suspicious Activity Reports" provide inadequate privacy safeguards and guidance on the definition of "suspicious activity," leading to violations of Americans' First Amendment and privacy rights, and to racial and religious profiling.