Sonic & Knuckles is the sequel to Sonic The Hedgehog 3. It is, to date, the only game to ever use a Lock-On Technology, the ability to connect another game cartridge into the original cartridge to unlock new content. The reason for this lock-on technology is because Sonic & Knuckles and Sonic 3 are actually one and the same game, and were split to cover cartridge production costs.
 Lock On
 Sonic the Hedgehog
Locking Sonic the Hedgehog onto the Sonic and Knuckles cartridge unlocks the full version of Blue Sphere, a mini-game from Sonic The Hedgehog 3 and Sonic and Knuckles. Additionally, almost any other Mega Drive cartridge slotted into Sonic & Knuckles will also unlock the blue sphere bonus stages aswell. The only difference is with Sonic the Hedgehog, the character animations on the title screen are animated, whereas they aren't with other games.
 Sonic The Hedgehog 2
 Sonic The Hedgehog 3
Locking Sonic The Hedgehog 3 onto the Sonic and Knuckles cartridge lets you play Sonic 3 and Knuckles, the updated version of both games which allows you to play as Knuckles in Sonic The Hedgehog 3 and Tails in Sonic and Knuckles.
The game has subsequently been ported to Microsoft's Xbox Live Arcade service and Virtual Console for Nintendo Wii, aswell as included in several compilations:
- Sonic Jam for SEGA Saturn
- Sonic & Knuckles Collection for PC
- Sonic Mega Collection for Nintendo Gamecube
- Sonic Mega Collection Plus for Nintendo Gamecube, Sony Playstation 2 and Microsoft Xbox
- Sega Genesis Collection/Sega Mega Drive Collection for Sony Playstation 2 and PSP
- Sonic's Ultimate Genesis Collection/Sega Mega Drive Ultimate Collection for Playstation 3 and Microsoft Xbox 360
- Sonic Classic Collection for Nintendo DS
The story continues on from the events of Sonic the Hedgehog 3, after beating Dr. Robotnik at Launch Base Zone, the partially reconstructed Death Egg falls to the Floating Island, along with Sonic and Tails, landing in the Mushroom Hill Zone. The pair continue their journey across the island to stop Dr. Robotnik and deal with Knuckles who is still working against them.
For the first time, Knuckles is now a playable character, he controls essentially the same as Sonic, although his jump doesn't reach as far. To counter this, he has the ability to glide through the air and climb walls. This means, depending on whether you pick Sonic or Knuckles, you get slightly different routes through the zones. Also, Knuckles' game ends at Sky Sanctuary Zone whereas Sonic's game continues on to the Death Egg Zone. Unlike the previous few Sonic games, there is no multi-player mode.
- Mushroom Hill Zone
- Flying Battery Zone
- Sandopolis Zone
- Lava Reef Zone
- Hidden Palace Zone
- Sky Sanctuary Zone
- Death Egg Zone
- The Doomsday Zone (Only accessible with Sonic when all Chaos Emeralds are collected)
- Special Zone
- Bonus Stage (Slot Machine)
- Bonus Stage (Magnetic Orbs)
- Number of Endings: 4
- How to obtain the endings: Beat Dr. Robotnik with or without all emeralds (Sonic) and Beat Super Metal Sonic with or without Emeralds (Knuckles). As Sonic, you fight an extra stage if you get all emeralds.
 Sonic’s Ending
- Bad Ending (don’t get all emeralds): Once you defeat Robotnik as you chase him down he’ll drop the Master Emerald. The Death Egg blows up and Sonic falls from space with the Super Emerald beside him but it stays stranded in space as Sonic falls alone. Tails catches him and makes a U-Turn around the fallen Angel Island which stays in the ocean and the credits roll as Sonic and Tails fly freely. At the end of the credits, Sonic jumps off and gives a #1 pose. The Sonic and Knuckles logo appears. Then it shows a small scene of Robotnik chuckling with the Master Emerald behind him.
- Good Ending (get all the emeralds): Super Sonic defeats Robotnik and snatches the Master Emerald. Sonic will fall from space alongside the Emerald and this time the Emerald stays with him as Tails flies by and catches Sonic and unleashes a rear claw to catch the Emerald. Tails will make a U-Turn and fly by the fallen Floating Island. The
island flashes and begins to rise out the water. The credits roll, as Sonic and Tails fly freely and at the end, Sonic jumps off the plane and disappears then reappears as Super Sonic and flies in the foreground with a “thumbs up”. The Sonic and Knuckles logo appears. Then it shows a small scene of a Robotnik droid rising from the rubble.
 Knuckles Ending
- Bad Ending (Don’t get all emeralds): Defeat Super Metal Sonic without all emeralds and the ground will crumble and both Knuckles and Metal Sonic fall. Sonic, flying the biplane, will catch Knuckles who is tired from the battle and flies back to the island and drops him off before flying away. During the credits, the Floating Island which has been tilting throughout the fight will fall down as the credits roll. It lands in the ocean as the Sonic and Knuckles logo appears. A small scene of Metal Sonic hoping onto the Super Emerald appears
- Good Ending (Get all emeralds): Defeat Metal Sonic with all emeralds and the floor will crumble and both Knuckles and Metal Sonic will fall. Sonic, flying the biplane, will catch Knuckles who is holding the Super Emerald and gives Sonic the “thumbs up” and both fly by the island where Sonic drops Knuckles off and flies away. The island which had been tilting throughout the fight will rise while the credits roll. It will stop eventually and it will show a glimpse of outer space. At the end of the credits, Knuckles jumps out of nowhere with his fist pumped and he Sonic and Knuckles logo appears.
- Hey Ho
- Barrier Eggman
- Stone Guardian
- Heat Arms
- Egg Mobile (Wrecking Ball)
- Flying Mecha Sonic
- Mecha Sonic
- Red Eye
- Death Ball
- Eggman Robo Rocket
Music from the game features in the following CD soundtracks: