When they arrive at Vision Enterprises, the puppies go inside a spacesuit machine and emerge wearing spacesuits. They follow the students to the spacecraft and climb aboard. Buddha and the rest of the Buddies spend time investigating the shuttle, but they soon find themselves sealed inside the craft with pilot Astro, and the shuttle launches into outer space.
Vision 1 is running low on fuel, so Mission Control sends the shuttle to an old research space station to refuel. When they arrive, Buddha and the others explore the space station, where they meet a dog named Spudnick, who is owned by Yuri, an astronaut living in the space station. When Yuri meets the puppies, he is happy to have them as company, but tries to trap them inside the space station. Spudnick and the Buddies ultimately escape, as does Yuri.
The shuttle then travels to the moon. Mission Control determines that the dogs are in space, and the news is broadcast on television for the children to see. The Buddies travel through a meteor shower as they embark on a dangerous voyage back to Earth.
When they land, the Buddies are rewarded for their bravery and honored with the title of "Space Buddies". Buddha gives Sam a rock he found on the moon, allowing Sam's wish of touching the moon to come true.