The Odysseus lander successfully touched down after a "nail-biting" descent.
Scientists back on Earth had to wait well past the expected touchdown time for confirmation there was a signal.
After a few tense minutes, applause and cheers erupted in the Houston control room.
One of the key aims of the IM-1 mission was to ensure safe-landing technologies worked, with NASA instruments measuring speed, distance and how much fuel was left in the tanks.
Now closer to the moon's south pole than any other craft, Odysseus will seek to determine if manned missions can communicate with Earth in the pole's extreme environments.
More NASA equipment is on board for contacting mission control, as well as navigation beacons dropped to help future missions.
Odysseus paves the way for IM-2, a second mission even deeper into the polar region, at the Shackleton Crater, aimed at finding ice.
Water would be able to hydrate astronauts and, by splitting the molecule, provide a source of oxygen to breathe and hydrogen that could be used as rocket fuel.
Together, the two missions ultimate goal is to create the conditions for NASA to send astronauts to the moon's south pole in 2026 under the Artemis programme.