Dedicated in memory of Joe Ranft.

Meant to be a sequel to Cars: Mater National (2007).

Once again, the open world has changed since Cars Mater-National (2007). All of the changes brought in, including the Ornament Valley Airport, Fillmore's Nature Park and the Upper Mine, have been removed, but some new changes came as well, which include a road running through the field in Ornament Valley, a new section tunnel in the Abandoned Mine in Tailfin Pass and the gates to Sarge's Boot Camp being open. Besides that, the 3 parts of Radiator Springs are now 1 world with no loading required to switch between any of the 2. Players can also explore 4 new locations outside of Radiator Springs, which are Radiator Springs Speedway, Santa Carburera, Autovia, and Motoropolis City.

Most of the new characters introduced from Cars (2006): The Video Game, a lot of which returned in Cars Mater-National (2007), do not return in Race-O-Rama. This includes Fletcher, Gerald, Papo, El Guapo, Vince, Barry, Sonny, Lenny, Buford and Judd. Of which, Papo and El Guapo did not return in Mater-National. On top of that, one character from Cars (2006), the film who appeared in the other 2 games, Lizzie, does not return here.

While Cars Mater-National (2007) brings back the music Bruno Coon composed for Cars (2006): The Video Game, none of it returns in Cars Race-O-Rama. It is instead replaced by a new score composed by Todd Masten. Even the main menu music is changed, making this the first of the 3 games not to have the Radiator Springs Theme as the menu music.

3 mini-games in Cars Race-O-Rama are similar to 3 mini-games from Cars (2006): The Video Game. There is Luigi's Tire Find, which is similar to Luigi to the Rescue. Another one, Sheriff's Chase is a lot like Sheriff's Hot Pursuit. The 3rd one, Tractor Stampede is similar to Tractor Tipping, one that returned in Cars Mater-National (2007), though it is a little different. Instead of trying to tip the tractors while sneaking around a tractor field, the goal is to drive around Radiator Springs to find and tip all the tractors.

There are a few other differences Race-O-Rama has from the past 2 games. A typical race now consists of 8 cars instead of 5. Paint jobs and bonus content are unlocked via winning races and earning points rather than purchased with points. Drifting has replaced powersliding and Lightning McQueen's body parts can be customized, not just his paint and tires. However, this game is also not available on the PC and GameBoy Advanced.

In the intro cut-scene the game's logo appears on a starting line. This is similar to how the Cars (2006) logo appears on a starting line in the first film.

Emma is the only character introduced in Cars Mater-National (2007) to return in this game, though only on the handheld versions.

The PlayStation 2 version of the game has some differences from the other console versions. A typical race has 4 cars instead of 8. There are only 2 Point to Point races instead of 5. The 3 parts of Radiator Springs have to load upon switching. Relay Races consists of 2 teams of 2 instead of 4 teams of 3. Only the first students from each academy are playable as opposed to all 8. Luigi and Trophy Girl are not playable outside of Guido Kart races, except for Luigi in Luigi's Tire Find. Bubba, Tater and Tater Jr. can only be played as in Rustbucket races. Doc Student 4, Fred, Lewis, Ginormous and Count Spatula are completely absent.

El Machismo's and Stinger's boss levels in the handheld versions are swapped in comparison to the console versions.