The race starts in a US city. Teams must then follow clues and instructions and make their way to checkpoints in cities around the world. Along the way, there are "Roadblocks", tasks that only one member of the team may perform, and "Detours", tasks that both members must perform.

In each leg of the race, one "Fast Forward" is available. A Fast Forward allows the first team to discover the Fast Forward to skip all further tasks and proceed directly to the checkpoint. Each team may use only one Fast Forward during the game.

There is a mandatory resting period of twelve hours at each checkpoint. Teams leave exactly twelve hours after they arrive, in the order in which they arrived. In most legs of the race, the last team to reach the checkpoint is eliminated (however, there are some non-elimination rounds). In some rounds, the first team to arrive wins prizes such as trips and cameras, which they receive at the end of the game.