In Need for Speed: The Run, the player steps into the shoes of Jackson "Jack" Rourke. After an occurrence leaves him with a bad standing with an crime organization, Jack becomes targeted and must flee for his life. The consequences leave him owing large amounts of money, which he cannot pay. His friend, Sam Harper, directs him to a massive street racing event called "The Run". The Run is a 3000 mile race across the United States, from San Francisco to New York City. She informs him the prize money, $25 million, is more than enough for his freedom but he would have to beat 200 other drivers to win. Not only that, but police as well as the criminal organization will stop at nothing to make sure he never makes it over the finish line.

Players can participate in an "underground world of illicit, high stakes racing" in a race from San Francisco to New York. There are stops through Las Vegas, Denver, Detroit, and tons of other locations. This is the first title in the Need for Speed series to use real locations. There is over 300 km of track, which is over three times what Need for Speed: Hot Pursuit had, making it one of the largest in the early series. Need for Speed Autolog, the franchise's social functionality, also included in Hot Pursuit and SHIFT 2 Unleashed, is back and tracks progression and lets you compare game stats with other players.

The Run also has quick time events, making the players exit their car and move on foot. These times aren't so harsh on players as the races are, and allow chances for them to pull through, but add an extra aspect to the game. The driving model of the game is somewhere between SHIFT and Hot Pursuit, as it's not so arcade as Hot Pursuit, but not as simulator as SHIFT. The Run has tons of cars, ranging from the usual muscle cars, street racers, and refined exotics. Each car is supposed to present a different challenge for the player. The damage system is very similar to Hot Pursuit. The cars can be changed and upgraded for their performance and visuals, like paint colors and body kits. In the game there are also "Aero Pack" kits, which upgrade style as well as performance.

The Run uses an XP system for unlocking cars and events. It also features a Rewind option which lets the player restart to their last checkpoint if they wreck their vehicle or miss an opportunity. Rewinds can be in limited supply, as the difficulty level dictates how many Rewinds you get. Easy has unlimited, normal 5, hard less, and impossible has no rewinds in addition to very, very difficult AI opponents.

With online matches, up to 16 players can play. They can party with friends, pick a playlist of challenges and complete on every stage of the game. Also, players don't have to wait in lobbies, even if the game they are wishing to join is in progress. There are different playlists, such as Supercar Challenge, NFS Edition Racing, The Underground, Mixed Competition, Exotic Sprint, and Muscle Car Battles. Most of the modes focus on different car varieties. Players can also use the reward system "The Bonus Wheel", which randomly selects a reward and the criteria to get it.