The Run takes place along the most dangerous roads in the United States of America from San Francisco to New York City. Players take the role of the protagonist Jack Rourke, a marked man in debt to the Mob, racing for his life to pay off the money he owes.
Stage 1 opens with Jack duct taped to the steering wheel of a Porsche 911 Carrera S that is being hoisted and dropped into a crusher by a crane.
Jack successfully escapes from the crusher and steals an Audi RS4 as he attempts to escape from The Mob. The Mob notices him and promptly pursues Jack. The pursuit ends when Jack crosses the railway before being involved in a collision with a train.
Jack meets long-time friend Sam Harper in a Chinese restaurant. As they begin to discuss Jack's troubles with the Mob it becomes clear that Jack and Sam both grew up together in the same neighbourhood.
Calvin Garrett walks past the two and this prompts Sam to let Jack know of a means of escaping his debt with the Mob. They head around back where they see Mila Belova leaving with her Run equipment.
Sam places a briefcase in a dumbwaiter lift which is then hoisted and returned back down with the case being replaced with a tablet device. The tablet is encoded with the route of The Run.
Jack heads to his garage in San Francisco and chooses a car to enter The Run with. The Police begin to shut down San Francisco and stop any racer from leaving the city as Jack makes his way to the start line of The Run at Nob Hill.
Jack has to reach 150th position upon reaching Las Vegas but must first leave San Francisco before the police close the Golden Gate Bridge. The long drive begins across the state of California.
After driving on the West Coast, passing San Francisco and the Altamont Pass, Jack enters the region of the Yosemite National Park. Jack soon finds a rival with a passion for more than just The Run itself.
Marcus Blackwell wants Jack out of the race and in a body bag after his escape from the crusher. He will do whatever he can at any point he can with his signature Aston Martin One-77.
Stage 3 begins as Jack enters Death Valley and ends in Las Vegas.
Jack has to race through a sand storm with severely reduced visibility in the centre of the lifeless Death Valley. He will also encounter Nikki and Mila as well as the highway police.
Reaching Las Vegas becomes all too real for Jack as he has to ditch his car after being nearly busted at a police roadblock. He's given a new goal; 50th position at Chicago.
Stage 4 opens with Jack going straight to the top of the police wanted list after his entanglement with them in Las Vegas. He has to cover ground in Nevada quickly and rushes out of Las Vegas in the dead of night.
Jack will cross the state of Nevada before the police catch up with him and his rivals in Zion National Park, Utah. It quickly becomes a desperate game of cat and mouse into Colorado and into the snowy clue of what is to come along the Million Dollar Highway.
Stage 5 opens with Jack running in the midst of a tight pack of racers along the icy and slippery Interstate 70. The snow proves to be the biggest enemy as Jack covers ground in Colorado.
The rivals start to push Jack to breaking point along the dangerous mountain roads as they climb higher and higher towards the inhospitable peaks. Jack reaches the summit of the Rocky Mountains in central Colorado and is faced with a conflict; turn back or risk it all along a closed highway.
The decision is made for him as a rival nearly runs him down and drives onto the closed highway. Jack has to beat the rival and make it to the other side of Independence Pass.
Stage 6 pits Jack against higher performance vehicles as these rivals made it through the Rocky Mountains before the snow storm. The narrow farmland roads of Nebraska, South Dakota and Minnesota are a speed run across middle North America.
The routes quickly become a series of split second choices with the tight packs of traffic and blind jumps resulting in several close calls for Jack.
Stage 7 is Jack's assault on Chicago and his desperate bid to reach position 50 before reaching the city. Jack has to fight off several rivals during his approach on Chicago through Wisconsin and Illinois.
The country roads leading to the Kennedy Expressway are dense and technical with little room for driver error. Jack's time along the expressway attracts the attention of the Mob and ultimately their attempt on his life in Lower Wacker, Chicago.
Stage 8 joins Jack as he tries to leave ruined Downtown Chicago and cross the remainder of Illinois with the Mob hot on his trail. Audi vehicles are Jack's only option.
The highways of Ohio get Jack back into The Run but the Mob has Jack in their sights and don't let up their aggression towards him. He has only one goal now; reach New York City in first place or lose it all.
The Mob push and push against Jack with him eventually being forced from his pursuit of first place in Cleveland, Ohio. The events in Cleveland's industrial district work in Jack's favour with Sam's connections giving him a final chance for victory.
Sam's connections have landed Jack in the presence of Uri, a mechanic for some very high-performance vehicles. Sam has arranged for Jack to take one of Uri's cars that will put him at level pegging with the rivals found in Stage 9.
Jack has to very little time to reach New York City and still a great deal of rivals to overtake. He finds himself zooming across the expressways of Pennsylvania and Interstate 68 of West Virginia before reuniting with the police in the forests of Maryland.
Stage 10 has Jack making his way to the front of the pack with the police closing in on him and his many rivals. Pennsylvania and New Jersey are in his way as he makes his final approach towards the east coast.
Jack faces off against Marcus Blackwell through the congested streets of Downtown New York City, the interconnected subway and the crowded dock yards.