Cruz has authored 70 United States Supreme Court briefs and presented 43 oral arguments, including nine before the United States Supreme Court. Cruz's record of having argued before the Supreme Court nine times is more than any practicing lawyer in Texas or any current member of Congress. Cruz has commented on his nine cases in front of the U.S. Supreme Court: "We ended up year after year arguing some of the biggest cases in the country. There was a degree of serendipity in that, but there was also a concerted effort to seek out and lead conservative fights."

In the landmark case of District of Columbia v. Heller, Cruz drafted the amicus brief signed by attorneys general of 31 states, which said that the D.C. handgun ban should be struck down as infringing upon the Second Amendment right to keep and bear arms. Cruz also presented oral argument for the amici states in the companion case to Heller before the United States Court of Appeals for the District of Columbia Circuit.

In addition to his success in Heller, Cruz has successfully defended the constitutionality of the Ten Commandments monument on the Texas State Capitol grounds before the Fifth Circuit and the U.S. Supreme Court, winning 5-4 in Van Orden v. Perry.

In 2004, Cruz was involved in the high-profile case, Elk Grove Unified School District v. Newdow, in which Cruz wrote a U.S. Supreme Court brief on behalf of all 50 states. The Supreme Court upheld the position of Cruz’s brief.

Cruz served as lead counsel for the state and successfully defended the multiple litigation challenges to the 2003 Texas congressional redistricting plan in state and federal district courts and before the U.S. Supreme Court, which was decided 5-4 in his favor in League of United Latin American Citizens v. Perry.

Cruz also successfully defended, in Medellin v. Texas, the State of Texas against an attempt by the International Court of Justice to re-open the cases of 51 Mexican nationals, all of whom were convicted of murder in the United States and were on death row. With the support of the George W. Bush Administration, the International Court of Justice argued that the United States had violated a treaty by failing to notify the convicted nationals of their opportunity to receive legal aid from the Mexican consulate. Texas won the case in a 6-3 decision.

The only thing worse than a liberal is a liberal that thinks they're a conservative.