The capsule splashed down 480 kilometers (300 miles) off San Diego at 12:40 ET (17:40 GMT).
"Splashdown... Orion back on Earth," NASA's livestream announcer said.
In the next minutes and hours, NASA specialists will recover the capsule and transport it to the John F. Kennedy Space Center in Florida. NASA will analyze the data collected over the 25-day mission in preparation for future crewed missions.
The unmanned Artemis 1 mission is key step toward NASA's goal of crewed lunar flights of the Orion spacecraft, with the first of them, Artemis 2, scheduled to launch in 2024. Artemis 2 is expected to be the first manned lunar mission since Apollo 17 in 1972, which is the most recent time people landed on the Moon.