Syndrome is the maniacal, delusional villain of the CGI Disney/Pixar film, The Incredibles. Originally a young boy named Buddy, he looked up to the superhero Mr. Incredible and wanted to be his sidekick. He showed a lot of enthusiasm and even demonstrated great technical prowess with a pair of jet-boots that he had designed himself. However, Mr. Incredible preferred to work solo and refused to let Buddy - who called himself "Incredi-Boy" at the time - join him on his patrols. After Buddy's interference prevented Mr. Incredible from apprehending a criminal, the hero put his foot down and had the police take him away. Buddy became enraged by his idol's dismissal of him and this resentment would fester into an absolute hatred toward all heroes.

Many years later, Buddy had amassed a vast amount of wealth and power by inventing hi-tech weapons and selling them to various governments around the world. Establishing a secret organization based on a remote island, Buddy took on the alias "Syndrome" and worked toward taking his revenge on his childhood idol, Mr. Incredible, and all other superheroes. He created a powerful combat robot called the "Omnidroid" which was capable of learning new tactics as it battled its foes. He lured various retired superheroes to his island stronghold where he pitted the Omnidroid against them. Many heroes were killed and those who had managed to defeat an Omnidroid would just be killed off by a succeeding model.

Eventually, Syndrome lured in Mr. Incredible, who - like most heroes - had been forced into retirement by the government following a string of lawsuits against heroes and wished to relive the glory days. Syndrome's partner Mirage offered Mr. Incredible a job and had him fight the latest version of the Omnidroid, which he defeated. However, Mr. Incredible was summoned back to the island weeks later and was attacked by an upgraded robot. It was then that Syndrome revealed himself and his past connection to Mr. Incredible. After a brief confrontation, Mr. Incredible escaped the Omnidroid and Syndrome by faking his own death. He would then sneak into Syndrome's base and access the villain's computer, discovering his plan. He was quickly discovered, however, and captured.

When Mr. Incredible's family came to the island to rescue him, they were also captured by Syndrome. He then revealed his master plan: to pretend to fight against his own Omnidroid as it attacked the city of Metroville and be revered as a hero. After achieving hero status, Syndrome planned to sell his inventions so that normal people would be able to live the dream of being a superhero, because if everyone is super, then no one will be.

Syndrome deployed the Omnidroid in Metroville and fought against it using a remote control on his gauntlet that caused the robot's attacks to fail. Being a learning robot, the Omnidroid realised that it couldn't beat Syndrome if he had the remote and so blasted it off of his arm. Syndrome was then knocked unconscious by the robot and when he later came to he discovered that the Incredibles had escaped his lair and destroyed the Omnidroid. Enfuriated by this upset, Syndrome flew ahead to the Parr family household where he found Bob (Mr. Incredible) and Helen (Elast-Girl) Parr's infant son Jack-Jack being cared for by a babysitter. Pretending to be a replacement sitter, Syndrome relieved the current sitter and awaited the Parrs to return home. When they arrived, he immobilised them with his gravity gauntlet and tried to abduct Jack-Jack. As he was about to board his aircraft, Jack-Jack suddenly revealed his shapeshifting powers and Syndrome was forced to drop him. Syndrome vowed to take Jack-Jack one day, but he would never have another chance as the engine turbine on his plane pulled on the villain's cape. Syndrome was sucked into the engine and ground to paste.

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