George's Cosmic Treasure Hunt begins in England when George's favorite friend, Annie, moves to America from England. After many days of missing Annie, she sends him an e-mail saying that there is an urgent matter and that he should come over to America. But instead of asking his parents, he asks his grandma who lets him do anything. Soon his grandma arrives at George's house and argues with his parents that he should go to America. The plan is George's parents, who are eco warriors, will go to an island that is nearly under water from rising sea levels and George and his grandma will go to America.
On the plane ride, George reads a book that Annie's father, Eric (who is an astronomer), had given him. When he lands in America, George meets a boy named Emmett and learns that Annie and Emmett hate each other. George also finds out that the big thing Annie mentioned in her e-mail was about a rocket launch with a probe inside that will land on Mars and search for life. When they get home Annie claims that she has received a message from the aliens, which says that if they don't follow a special set of rules, Earth will blow up.
George and Annie decide to take action, but they also need to figure out a way to use Emmett. To help the Earth, they need to go across the Universe. To do that, they need to open up a broken computer called Cosmos, which can open up portals through the Universe. Emmett is a computer genius who quickly fixes Cosmos. On the day of the launch of the Mars probe, they sneak into a room at the launch site. George and Annie put on space suits, and Emmett opens up a portal to Mars.