Knuckles the Echidna is the strong, serious guardian character from the Sonic the Hedgehog games, which makes his panicked Knuckles Oh No delivery funnier than a normal reaction. The two word line was clipped from his in game voice work and shared online as a standalone reaction, then spread through meme edits, gaming videos and soundboards. Its brevity helped it travel, because it fits almost any small disaster without needing context. It is still used because that contrast between a tough character and instant dread remains easy to understand.