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When Dr. Eggman was creating another hedgehog called Cinos, an evil clone of Sonic, with red fur, blue shoes, black gloves and socks, yellow eyes, and silver buckles, Metal Sonic helped him to trace the body of Sonic. Dr. Eggman also teamed up with Mario's enemy Bowser to create a golden watch, which can hypothize/brainwash anyone. After completing Cinos, Dr. Eggman abducts Sonic, Tails, Knuckles, Amy, Cream & Chesse, Rouge, Espio, Shadow,Silver, Blaze, Vector and Charmy and takes them to his Lab, with Bowser stealing all the Power Stars and Grand Stars from Princess Peach's castle with the help of Bowser Jr. After kidnapping Baby Mario, Baby Luigi, stealing Donkey Kong and Diddy Kong's banana hoard and Wario and Waluigi's money, Dr. Eggman calls Cinos to take hold of them, then brainwashes Sonic and his friends. After being brainwashed, Sonic, Shadow and Silver each get a dark form after draining the Chaos Emeralds' power completly (leaving all the power of the Emeralds useless) Knuckles, Espio and Vector each obtain an outfit similar when Knuckles was an Enerjak, Amy, Blaze and Cream & Chesse turn into loose resemblances to Rouge, wearing her outfit and makeup, while their hair is much longer, and Tails, Charmy and Rouge's eyes turn from their normal color to red. Big the Cat finds out and runs off to the Mushroom Kingdom. After being told this by Dixie Kong, Birdo and Toadette, Mario and Luigi, along with Peach, Daisy, Yoshi, Wario, Waluigi, Donkey Kong, Diddy Kong, Toad, Koopa and Shy Guy, head to Bowser and Dr. Eggman's lab for revenge.
The group start their adventure in the Mushroom Kingdom, after collecting some Stars, they find Gamma and Omega who tells them what happened to Sonic and his Friends and that they've seen Larry Koopa at the fortress, after defeating him, they get to the Castle and battle Petey Piranha and after defeating him, they abord to the Airship and restore Knuckles, Vector and Espio and head to Sandy Desert where they defeat Morton Koopa Jr., The Bob-omb King and restore Amy, Cream and Chesse and Blaze and head to Icy Snow where they defeat Wendy O. Koopa, King Boo and restore Tails, Charmy and Rouge and they go to Flower Beach where Tikal tells them about Cinos and defeat Iggy Koopa, The Whomp King and Cinos who is forced to flee after his defeat, and then head to Posion Jungle where they defeat Roy Koopa and Goomboss as they continue threw the forest they run into Evil Silver and Evil Shadow, The two try to capture the group so they can get them to be brainwashed themselves and fight them, but the group prevail, afterwards Shadow and Silver are restored and the group then head deeper into the forest, end up fighting Evil Sonic and restoring the blue blur back to normal.
With Sonic and his friends restored to their normal selfs, Mario and the others continue to Star Mountain to collect more Stars and defeat Lemmy Koopa, Shadow Mario and Bowser Jr. and they head to Sky Fortress and defeat Ludwig von Koopa, Gooper Blooper and Metal Sonic, and they make their way to Bowser's Castle where they defeat Boom Boom, The Reznors, The Deadly Six and Dry Bowser, but Bowser escapes in his clown car to Eggman's Lab and the heroes go there and collect all the Chaos Emeralds, Grand Stars and defeat Pom Pom, Tiki Tong, Hisstocrat and Eggman Nega, but Dr. Eggman escapes with Orbot and Cubot in his Egg Mobile to Rainbow Planet and the heroes follow them to collect Baby Mario & Baby Luigi, the bananas and the money (which Jet, Storm and Wave somehow stole from Dr. Eggman with help from Rosalina) and defeat Mephiles, Motley Bossblob, King K. Rool and finaly defeat Bowser and Dr. Eggman in their Madzilla Robot and Mario and Friends go back to the Mushroom Kingdom while Sonic and and Friends go on their next adventure.
- Mario: He plays like Super Mario 3D Land. He can stomp most enemies, use his Hammer to hit them, use his spin attack and can spray water at them using F.L.U.D.D.
- Luigi: He plays like Luigi's Mansion Dark Moon. He can jump higher and run faster than Mario and can use the Poltergust 5000 to suck up ghosts.
- Yoshi: He plays like Yoshi's New Island. He can flutter jump, swallow enemies with his tounge, ground pound and throw eggs at them.
- Toad: He plays like Super Mario 3D World. He can run faster than Luigi and pick up objects and throw them at enemies.
- Donkey Kong: He plays like Donkey Kong Country Returns. He can attack enemies with his giant punch, make the ground shake with his hand slap, pick up objects and throw them faster than Toad and throw DK Barrels at enemies.
- Diddy Kong: He plays like Donkey Kong Country: Tropical Freeze. He can shot at enemies with his Peanut Popgun and reach places others can't with his Barrrel Jet Pack.
- Wario: He plays like Wario World. He can ground pound harder than Yoshi, punch harder than Donkey Kong and break black blocks with his wario punch and dash at enemies with his dash attack.
- Waluigi: He plays like Mario Tennis Open. He can throw Bom-ombs at enemies and can whack them with his Hammer.
- Sonic the Hedgehog: After the player defeats Evil Sonic, Sonic will be unlocked. Sonic's the fastest character in the game. He plays like Sonic Lost World.
- Miles "Tails" Prower: After the player defeats Evil Tails, Tails will be unlocked. He plays like Sonic Adventure.
- Knuckles the Echidna: After the player defeats Evil Knuckles, Knuckles will be unlocked. He plays like Sonic Adventure 2.
- Amy Rose: After the player defeats Evil Amy, Amy will be unlocked. Amy can use her hammer to hit her enemies with it. she plays like Sonic The Hedgehog (2006).
- Shadow The Hedgehog: After the player defeats Evil Shadow, Shadow will be unlocked. He plays like Shadow The Hedgehog.
- Silver The Hedgehog: After the player defeats Evil Silver, Silver will be unlocked. He plays like Sonic The Hedgehog (2006).
- Blaze The Cat: After the player defeats Evil Blaze, Blaze will be unlocked. She plays like Sonic Rush Adventure.
- Cream The Rabbit & Cheese The Chao: After the player defeats Evil Cream & Cheese, Cream & Cheese will be unlocked. They plays like Sonic Advanced 3
- Bowser & Dr. Eggman: The main villains in the game. They brainwash Sonic and his friends and create Cinos to destroy Mario & Co.
- Cinos the Hedgehog: Sonic's evil counterpart, with red fur. He was created by Dr. Eggman to destroy Mario & Co. He first appears in this game.
- Bowser Jr & Metal Sonic: They can be seen helping Bowser & Dr. Eggman creating Cinos.
- Big the Cat: After knowing what had happened, Big (with Froggy) quickly tells everyone about the brainwashed Sonic and his friends.
- E-102 Gamma: He quickly tells everone about the brainwashed Sonic and his friends, along with Big.
- Tikal the Echidna: While she is walking alone, she meets Cinos. Tikal (with a couple of Chao) then tells everyone about Cinos.
- E-123 Omega: He appears in Gamma's side, telling everyone about Dr. Eggman's creation, Cinos.
- Maria (cameo): She can be seen swimming in a lake, wearing a beautiful bathing suit.
- Sparky the Porcupine (cameo): He can be seen activating an old lighthouse.
- Froze the Dog (cameo): Froze can be seen working in a shaved ice stand.
- Plasma the Chipmunk (cameo): Plasma comes to Chelsea's house, having some tea with her.
- Chelsea the Hedgehog (cameo): Chelsea let Plasma have some tea with her.
- Nebula the Hedgehog: after learning about the brainwashed Sonic and his friends, Nebula decides to join the others in the battle against Bowser and Eggman, she appears a few times as an ally.
Like in New Super Mario Bros. U The worlds are named but there are 10 instead of 8 this time.
- World 1: Mushroom Kingdom (5 Levels) Boss: Evil Knuckles, Evil Espio and Evil Vector
- World 2: Sandy Desert (6 levels) Boss: Evil Amy, Evil Cream & Chesse and Evil Blaze
- World 3: Icy Snow (8 levels) Boss: Evil Tails, Evil Charmy and Evil Rouge
- World 4: Flower Beach (10 levels) Boss: Cinos the Hedgehog
- World 5: Posion Jungle (5 levels) Boss: Evil Silver, Evil Shadow, Evil Sonic (true boss)
- World 6: Star Mountain (10 levels) Boss: Bowser Jr.
- World 7: Sky Fortress (15 levels) Boss: Metal Sonic
- World 8: Bowser's Castle (7 levels with the Chaos Emeralds) Boss: Dry Bowser
- World 9: Eggman's Lab (8 levels with Grand Stars that will restore the Chaos Emeralds) Boss: Eggman Nega
- World 10: Rainbow Planet (9 Levels with bananas and money and the babies) Boss: Bowser & Dr. Eggman (last)
- Chao World: Play as any character you've unlocked. You can play with Chao in this area.
- 10 Coin (Gives you 10 coins)
- 100 Coin (Gives you 100 coins and a 1-Up)
- Warp Pipe
- Clear Pipe
- Super Mushroom (Turns you into Super Mario)
- Fire Flower (Turns you into Fire Mario)
- Super Star (Makes you Invincible Mario for 30 seconds)
- 1-Up Mushroom (Gives you a extra life)
- POW Block
- Posion Mushroom (Makes you lose your power up)
- Super Leaf (Turns you into Raccoon Mario)
- Statue Leaf (Turns you into Tanooki Mario)
- Winged Cap (Turns you into Winged Mario for 60 seconds)
- Metal Cap (Turns you into Metal Mario for 60 seconds)
- Invisible Cap (Turns you into Invisible Mario for 60 Seconds)
- Mega Mushroom (Turns you into Mega Mario for 30 seconds)
- Mini Mushroom (Turns you into Mini Mario)
- Blue Koopa Shell (Turns you into Shell Mario)
- Star Coin
- Green Star
- Red Ring (Makes 8 Red Coins appear)
- Life Mushroom (Adds 3 health sections to Mario's health meter)
- Bee Mushroom (Turns you into Bee Mario)
- Boo Mushroom (Turns you into Boo Mario)
- Lava Mushroom (Turns you into Lava Mario for 30 seconds)
- Ice Flower (Turns you into Ice Mario)
- Rainbow Star (Turns you into Rainbow Mario for 30 seconds)
- Spring Mushroom (Turns you into Spring Mario)
- Red Star (Turns you into Flying Mario for 60 seconds)
- Star Bits
- Launch Star
- Pull Star
- Star Chip
- Propeller Mushroom (Turns you into Propeller Mario)
- Penguin Suit (Turns you into Penguin Mario)
- Propeller Block
- Glow Block
- Snow Mushroom (Turns you into Snow Mario for 30 seconds)
- Cloud Flower (Turns you into Cloud Mario)
- Rock Mushroom (Turns you into Rock Mario)
- Boomerang Flower (Turns you into Boomerang Mario)
- Invincibility Leaf (Turns you into White Tanooki Mario)
- P-Wing (Turns you into White Raccoon Mario)
- Propeller Box
- Question Mark Box
- Gold Flower (Turns you into Gold Mario)
- Gold Wing
- Gold Mushroom (Gives you 50 coins)
- Gold Block
- Super Acorn (Turns you into Flying Squirrel Mario)
- P-Acorn (Turns you into Power Squirrel Mario)
- Green Ring
- Warp Box
- Blue Ring (Makes Blue Coins appear)
- Cat Bell (Turns you into Cat Mario)
- Double Cherry (Creates a double of you)
- Cannon Box
- Light Box
- Plus Clock (Adds units of time to the time limit)
- Koopa Shell
- Skate Shoes
- Goomba Mask
- Ring (Lets you take a extra hit)
- Ring Box (gives you 10 extra rings)
- 10 Ring (Adds 10 rings to your ring counter)
- 1-Up Box (Gives you a extra one up)
- Shield Box (Puts a shield around you)
- Electric Shield Box (Lets rings come to you)
- Fire Shield Box (Makes you inmune to fire attacks and lets you fire dash)
- Bubble Shield Box (Makes you inmune to water attacks and lets you bubble bounce)
- Speed Shoe Box (Makes you run super fast)
- Invincibility Box (Makes you invincible for 30 seconds)
- White Wisp (Fills up your Boost gage)
- Cyan Wisp (Turns Sonic into the Cyan Laser)
- Yellow Wisp (Turns Sonic into the Yellow Drill)
- Orange Wisp (Turns Sonic into the Orange Rocket)
- Blue Wisp (Turns Sonic into the Blue Cube)
- Green Wisp (Turns Sonic into the Green Hover)
- Pink Wisp (Turns Sonic into the Pink Spikes)
- Purple Wisp (Turns Sonic into the Purple Frenzy)
- Red Wisp (Turns Sonic into the Red Burst)
- Violet Wisp (Turns Sonic into the Violet Void)
- Indigo Wisp (Turns Sonic into the Indigo Asteroid)
- Crimson Wisp (Turns Sonic into the Crimson Eagle)
- Magenta Wisp (Turns Sonic into the Magenta Rhythm)
- Black Wisp (Turns Sonic into the Black Bomb)
- Ivory Wisp (Turns Sonic into the Ivory Lightning)
- Grey Wisp (Turns Sonic into the Grey Quake)
- Amy's alternate costumes are Rouge, Princess Peach, Princess Daisy, Tikal, Cream and Blaze. (Buy them in Chao Shop)
- Funky Kong, Boo, Dry Bones and Hammer Bro are considered to be playable in Chao World.
- Completing the game will unlock Rosalina, Birdo, Toadette, Dixie Kong, Big, Omega, Gamma and Jet.
- The game has a mixture of 3D and 2D levels.