Eleven teams from previous seasons take off on a new adventure around the world. The lively mix of teams includes a past winning team, a diverse of group of players and many familiar faces both hated and loved. The teams take off from the starting line at Miami, Florida and each takes one of two flights departing for Quito, Ecuador. Tension builds early on as one team lies to another about the arrival times of the flights. Once in Ecuador, the teams takes taxis to the Plaza San Francisco and then travel to Pim's Restaurant, three-miles away, where they receive one of three fifteen-minute staggered departure times for the next morning. That morning, teams make their way to the Hacienda Yarahurco in the Cotopaxi National Park, guided by a provided map and with the advice to head to the north entrance. Once teams arrive, they take part in a Detour that involves either searching for missing items from the uniform of a soldier or wrangling and then grooming a horse. Several teams find themselves at the wrong end of the massive park, a costly mistake for one team that ultimately leads to their elimination.

The teams take off from their Pit Stop, an active volcano at Mirador Cotopaxi. They receive a clue instructing them to travel 7,400 miles to Santiago, Chile and then take a taxi for 17 miles to the headquarters of Codelco. There, the teams take part in a Roadblock that is ultimately rendered largely meaningless when they all make the same flight traveling 230 miles to Chuquicamatta in Calama, Chile. Once at their destination, the teams put on their safety gear and take part in a Detour that requires them to choose between two tasks traditionally involved in Chilean mining operations. The teams then use marked vehicles to travel the treacherous Valley of the Moon before emerging on safer ground and heading for the Pit Stop at the Valley of the Dead. One team makes a crucial mistake by failing to properly read a clue and posted signs regarding a speed limit. Due largely to this mistake, they fall behind and are eliminated from the race.

The nine remaining All-Star teams receive a clue that directs them to travel from their Pit Stop at the Valley of the Dead in Chile four miles to a church in the village of San Pedro de Atacona by the same name. There, they find that they must fly 800 miles to Puerto Montt and then drive 30 to fishery in Metri. As teams maneuver for flights, several find themselves behind when they are unable to catch an early flight, but catch a small break when the flight arrives slightly early. At the fishery, one member of each team completes a Roadblock that requires them to transfer fish from one tank to another. Afterwards, the teams travel fifty miles to Petrohue and find La Maquina, a popular spot for adventure spots. All teams take part in a watery Detour and one loses time-but not position-after neglecting to pick up a clue. Ultimately, one team is unable to make up time after struggling to find the Detour location and is eliminated from the race.

Eight All-Stars teams take off from their Pit Stop at the Playa Petrohue and receive a clue instructing them to fly 800 miles to Punta Arenas, Chile and then take taxi fifteen miles to Lord Lansdale's shipwreck. The teams arrive on two flights and take part in a Detour, where lack of attention-to-detail allows teams on a later flight to catch up to teams that had gained a lead. One team experiences a near-meltdown during the Detour, but regroups and rallies by switching tasks. Meanwhile, a previous top team finds itself falling behind. The teams take two charter flights leaving three hours apart and find themselves faced with a Roadblock that requires one member of each team to sort through mail. As reward, each team receives a message from a past team, some negative and some positive. One team lies to another, hoping to gain an advantage. This team, however, is ultimately unable to recover from falling behind and is eliminated from the race.

The remaining seven teams take off from their Pit Stop at the "End of the World" in Argentina and travel to the nearby Marshall Mountain chain, where they hike a half a mile and then use an avalanche beacon to search for another containing a clue. The clue instructs them to fly 7,000 miles to Naputo, Mozambique. Though teams are provided with tickets arriving at 3 P.M., all successfully negotiate tickets for an earlier flight arriving at 9 A.M. They then travel 45 miles via provided cars to the Apopo Training Field where one member of each team takes part in a Roadblock involving trained rats. After completing this task, they then face a Detour that involves either fancy fingernail-care or heavy lifting. Teams race for the Pit Stop, where two teams have a foot-race that leads to virtual tie. One team arrives last but is delighted to learn that they are not eliminated.

Teams take off from the their Pit Stop at Fort Aleza in Maputo, Mozambique and are instructed to fly to Dar Es Salaam, Tanzania, 1,400 miles away. A scramble for flights immediately begins and teams find that flight placement in this leg plays a major role in where they will ultimately end up. One team makes a risky move in opting to take standby-only seats on a flight, which ultimately gains them valuable time and allows them to arrive in first. One team is disappointed when they believe they have secured seats on a flight, but are removed, told that they had been given the seats in error. Once in Mozambique, teams takes one of four dhows (ferries) into Zanzibar, where they then take part in a Roadblock that requires them to choose between either a task that "taxes the mind" or one that "taxes the muscles." They then traveled 15 miles by taxi to the "bush country" of Kikungwi for a Roadblock that involved skill and accuracy. In a leg that involved a great disparity between first and last, a close finish led to the elimination of another team.

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The teams are instructed to travel from their Pit Stop at the Pieskowa Skała castle in Krakow, Poland and fly to Kuala Lumpur, Malaysia, over 5,500 miles away. Once there, the teams search for the best way possible to get to the Batu Caves, traveling by both bus and train. A Detour proves frustrating for some teams and even more frustrating for another, who first has to wait out a Yield before making their way to their chosen task. Stress and frustration cause two teams to switch Detour tasks, which one arguing over the specifics of what's required for a particular task. After completing the task, the teams then travel by taxi six miles to Taman Sri Hartamas and locate a newspaper. A Roadblock proves physically tiring for several of the Racers, but assistance from locals and perseverance see them through the task. Ultimately, a missed flight connection dooms one team. Unable to quickly attain alternate travel, they fall far behind and do not arrive in Malaysia until well after the other teams, leading to their elimination.

The four remaining teams compete in the tenth leg. At the Pit Stop at the "Mansion on the Hill" in Kuala Lumpur, Malaysia, they receive a clue instructing them to fly approximately 1,500 miles to Hong Kong. Teams find themselves in a struggle for standby flights, with confusion and bitterness regarding line order. Following Dustin and Kandice's choice to use the Yield in the previous leg, the other teams align against them in the hopes of becoming the final three. Once in Hong Kong, the teams travel 22 miles to a laundry. A high-speed fast forward catapults one team to first place, but they find themselves in dire financial straits. The remaining teams all take part in a physically demanding climbing task for the Detour, though one waffles as to which task to choose before making their ultimate decision. This team then makes a critical error when instead of taking the Star Ferry to Hong Kong Island, they instead end up on a completely different ferry to Kowloon. After kicking down doors in the Roadblock and carefully pulling Travelocity gnomes across a pond, the teams head for the Pit Stop, the Hong Kong Jockey Club. The two trailing teams face heavy traffic and navigation confusion and one receives some relieving news upon arriving at the Jockey Club.

The four remaining teams set off from the tenth Pit Stop at the Hong Kong Jockey Club and travel forty miles away to Macau, riding on turbojet ferries. The teams are pleased to find that they are able to procure these ferries early in the morning, but less pleased when they find that their next destination, the Macau Tower, does not open until 8 A.M. When one team faces financial difficulties, they make a deal to Yield another team in order to procure much-needed cash. Once the Tower opens, one member of each team takes part in a Roadblock that involves the highest jump in the history of the show. After completing this task, the teams took a taxi to the Lou Lim Ioc Garden, where Detour tasks tested either their ability to pay attention to detail or their mettle at navigation. Upon completing this task, all teams were faced with the challenge of driving a mini-moke. Navigating this unfamiliar vehicle to the Pit Stop proved a major challenge for some teams, and in the end, one checked in last, only to receive a major surprise.

Teams take off from their Pit Stop at the Triho de Taipa Pequena 2000, receiving a clue to fly 7,500 miles to the island of Guam, then drive nine miles to Anderson Air Force Base. A struggle for flights results in one team only narrowly making it onto the first flight to Guam with the other three teams. Once at the Air Force Base, the teams are escorted by naval officers to a control tower, where they receive a clue for a Detour in which they can choose to test their mettle at cleaning, or dare for some high-flying. On the way to the next task at the U.S. Naval Base, one team finds itself lost and needs local help in order to locate the destination. As other teams complete the Roadblock task, they fall behind. Still behind as others are struggling to complete the Roadblock task, a search-and-rescue, they try their best, but fear elimination. In the end, they are ultimately unable to catch up and check in last at the Pit Stop, Fort Soledad, and are eliminated from the race. The final three teams are left to race in the finale for the one million dollar prize.

The All-Stars final three -- Dustin & Kandice, Eric & Danielle, and Charla & Mirna -- compete in the final leg to determine who will win the one-million-dollar prize. The teams take off from their Pit Stop in Guam and are instructed to fly 3,500 miles to Honolulu, Hawaii. One team secures an early flight, but the advantage is largely neutralized when the teams must sign up for charter flights leaving ten minutes apart in Hawaii. The teams travel to Kaumalapau Harbor via Jeeps and find themselves in involved in a Detour that tests their ability at a skill either above or below water. All teams then travel to Shipwreck Beach and crossing rocky terrain, face a challenging kayaking task to retrieve their next clue. Ultimately, all teams board the flight to Oakland, California, en route to their final destination city of San Francisco. A final task tests the ability of the racers to think like their partners. When one team proves rather more adept at it than the others, it turns out to be advantage they need to secure victory. They cross the finish line in San Francisco's Botanical Garden first and become the winners of The Amazing Race: All Stars.