The player takes control of one of three strongmen, the titular "Combatribes": Berserker, a blond-haired man in a blue outfit who is endowed with a balance of speed and strength; Bullova (who takes his name from an Indian battle axe), a black man in a yellow outfit who is the strongest of the trio, but also the slowest; and Blitz (short for "blitzkrieg"), is a long-haired man in a red outfit who has the most agile attacks, but lacks the strength of the other two characters. The heroes boasts a variety of unique techniques in addition to the standard punch and kick combos such as stomping on an opponent, swinging them by their ankles, kicking them on the ground, slamming their faces into the pavement and even the ability to slam the heads of two opponents together. The player can also pick up certain large-sized objects (parked motorcycles, go-karts or pinball machines) and toss them over enemies. The game can be set up so that it can be played by up to two or three players simultaneously. In the 2-Player version of the game, the player is asked to select their character at the character select screen, whereas the 3-Player version has each player already assigned with a corresponding character.

The game is composed of six different stages (or "Acts" as they're referred within the game) set in unique locations, each featuring a themed gang. The majority of the stages are composed of a single playing field where the player must take on a set number of underlings before facing the gang's leader, similar to Renegade. Some stages break away from this formula by having more than one level. The gangs the player faces are in order: a biker gang in Times Square, circus performers in Coney Island, roller skaters in a dance club, a punk gang in a baseball stadium and a militia in a high-rise building.

The final stage is a boss rush against all the previous gangs while chasing a big crime boss in the harbor. After the gangs are defeated once again, the crime boss is killed by a female cyborg, Martha Splatterhead. Martha then engages the player in a final battle. If two or three players are present by the start of the final battle, an additional clone or two of Martha will appear to match the number of players. All Marthas must be defeated to complete the game.

The Super NES version of The Combatribes makes a few changes to the game. The game now features story sequences before and after boss battles, as well as an opening intro explaining the plot and a different ending. The gameplay remains the same, with the character's health now represented by a life bar instead of numeric values. There are no weapons to be picked-up and thrown in the SNES version, the stages are simpler and some of the enemy characters are missing. The bikers who carried broken bottles in Act one no longer drop their weapons after being sufficiently damaged. The flame-eating boss of Act two ("Salamander") normally loses range on his torch attack the more damage he takes, while the console version keeps him at full strength until he drops it.

Two player moves are also missing: the ability to pick up and carry enemies around, and the ability to repeatedly kick downed opponents. The fifth stage is composed of a boss rush against all the previous gangs before facing the Slaughter Troops. The sixth and final stage is simply a final battle against Martha Splatterhead set atop the rooftop of a high-rise building. The crime boss from the arcade version is missing in the SNES port, which identifies Martha as the leader of the gangs early on instead. Additionally, only one Martha will fight the player, regardless of the number of players present at the final stage.

In addition to the main game, there's a one-on-one versus mode similar to the one featured in the NES version of Double Dragon. The player can perform Street Fighter II-style special techniques including fireballs and block attacks with some characters. The game's enemies and bosses can also be used by inputting passwords given in the main game.

The console port was censored from the arcade version, with the blood splattering effects from certain attacks (like being hit with knives) being completely removed.

The North American version of the game was further censored, with the blood on enemy's faces during cut scenes being recolored white to look like saliva, sweat and tears. One of the bosses, a cyborg general named Swastika, was renamed "M. Blaster", to remove obvious references to Nazism. The fifth stage gang is renamed "The Demolition Troops" (instead of "The Slaughter Troops"). Additionally, in the Virtual Console re-release, the gang "Ground Zero" was renamed to "Guilty Zero".

An album containing the original soundtrack for the arcade versions of Double Dragon 3: The Rosetta Stone and this game was released by Pony Canyon in Japan, titled Double Dragon 3/The Combatribes. It was released on June 21, 1991 and its catalog number is PCCB-00065. Tracks 13 to 21 are taken from The Combatribes.

1. "The Rosetta Stone" (arranged version)
2. "The Rosetta Stone"
3. "To the Dragon World"/"In America"/"The New Black Warriors"
4. "Jim's Theme"/"The Way of Sōsetsuken"
5. "To the Dragon World"/"In China"/"Li's Theme"
6. "To the Dragon World"/"In Japan"/"Ranzou's Theme"
7. "To the Dragon World"/"In Italy"/"Giuliano's Theme"
8. "To the Dragon World"/"The Enchanted Forest"/"Enter the Dragon"
9. "The Fearsome Goblin"/"Roppe, the Stone Man"/"Hiruko's Trap"
10. "Awakening of the 2,000 Years Old Demon"/"Cleopatra's Theme"
11. "To the Children of the World"
12. "Play Version"
13. "The Final Battle" (arranged version)
14. "Title Roll"/"The Motorcycle Nuclear Warheads"/"2X4 Fatman"/"Go to next Act"
15. "Amusement Park Nightmare"/"Persian Warlord"
16. "The Slash Skate Screamers"/"Destroy Overdrive"
17. "Place of S.O.D."/"War Paint"
18. "The Slaughter Troops"/"Swastika is Cyborg"
19. "The Final Battle (Martha Splatterhead)"
20. "Ending (Out of Somewhere)"/"Staff Roll (Rest in Peace)"
21. "Play Version"