
The Super Heavy booster separated as planned but failed to complete its boost-back burn before falling uncontrolled into the Gulf of Mexico. SpaceX had not planned to recover the booster.
Musk praised the mission on X, calling the flight "epic."
"You scored a goal for humanity," he said.
The launch came a day after an aborted attempt caused by a hydraulic issue involving the launch tower arm. Musk said the problem was fixed overnight.
Friday's mission was Starship's 12th test flight and the first in seven months. The upgraded vehicle stands more than 407 feet (124 meters) tall when fully stacked.
Starship is central to NASA's Artemis program, which aims to return astronauts to the Moon before the end of the decade. SpaceX is developing a lunar landing version of the spacecraft under contract with NASA, while rival Blue Origin is pursuing a competing system.
NASA administrator Jared Isaacman, speaking before launch, said: "We're looking forward to seeing this fly, because hopefully at some point in the not-too-distant future we're going to join up in Earth orbit."
After the flight, Isaacman congratulated SpaceX on X for "a hell of a V3 Starship launch."
"One step closer to the Moon...one step closer to Mars," he said.