Dregg is first seen on the planet Varanon waiting in line at a bargaining space port on Varanon when the Ninja Turtles accidentally rammed into him while trying to elude angry sales aliens. Dregg was infuriated by this, and he even knocked Leonardo away when he offered to help him up. Dregg then asked them if they know who he was. When they denied, he explained who he was and threatened to kill them all. After Casey Jones taunted Dregg he, was attacked and nearly eaten by him. The turtles knock him Down to save Casey, but in the process also broke Dregg's container of expensive star spice, making him even more angry. He orders two of his Robug Vreen to attack them, but the turtles and April manage to defeat them. An Infuriated Dregg then tries his own hand against the turtles. He proves to be a powerful that even the seven of them can't seem to beat, so they decided to retreat into space using the Ulixes to evade him. However, Dregg follows them in his own spaceship, the Hornetron, which then lays "eggs", sending more Robug Vreen to attack ship while it is preparing for a Tachyonic Warp. One of which manage to get inside and attacks them all. They defeat it, however, and manage to use the ship's Tachyonic Warp to escape Dregg. Afterwards, Dregg swore that he would hunt the Turtles down and eradicate them.
Dregg managed to follow their movement to the Ice planet they were trapped on in The Moons of Thalos 3 But by the time he reached the ice world, the heroes were long gone. While there Dregg set up a meeting with the the alien shark bounty hunter, Armaggon. Dregg then hired Armaggon to kill the turtles and bring him their shells. Later on, Dregg contacted Armaggon to alter the deal to bringing the turtles to him alive so he can have the pleasure of annihilating them himself. Armaggon agreed to do it for double the pay.
Vrax Belebome informs Lord Dregg that the turtles are searching for a black hole generator, and assures him that any minute, the Neutrinos will be back with all kinds of info on it, as well as anything else the turtles are hiding. He is quickly proved wrong however, as the turtles angrily confront him before he even finishes his conversation.
Dregg is contacted by the bounty hunter he hired previously, Armaggon, with good news. That news being that Armaggon has commandeered the Ulixes, taking the Turtles, April, Casey, and the Fugitoid prisoner and capturing the first piece of the Heart of Darkness. Dregg is very proud of Armaggon, but when he adds on that this will make up for Armaggon's previous screw-ups, Armaggon quadruples his pay, much to Dregg's anger. Later, Dregg and his Vreen drones arrive to rescue Armaggon, who had been captured by Hiidrala and her Daagon, while also demanding the second piece of the Heart of Darkness, threatening to devour Hiidrala and her Daagon to get it. When Hiidrala refuses, a battle ensues. Dregg uses one of his claws to free Armaggon to join the fight, and after managing to overpower Donatello and Leonardo, goes after Hiidrala herself, covering her face with one of his claws, leaving her wide open to a point-blank attack from a missile launched from his chest. However, Leo takes the missile himself, the force of the blast knocking Dregg to the ground, allowing Hiidrala to remove Dregg's claw and then summon her guardian, the Cthugga, which devours Dregg and Armaggon whole. With Dregg gone, his Vreen are unable to act independently of each other and withdraw. Luckily for Dregg and Armaggon, Dregg's ship, the Hornetron, locates the Cthugga's lair and when the Cthugga opens its mouth, the Hornitron launches dozens of Vreen eggs into its mouth, where upon hatching, are able to safely fly Dregg and Armaggon out of the Cthugga. While the Cthugga retreats, Dregg returns to the Hornetron's cockpit, and chuckling evilly, vows that vengeance will be his as he and Armaggon set off to go after the Turtles again.
With Armaggon's help, Dregg captures the Turtles' Salamandrian allies, Y’Gythgba and G’Throkka. Using the threat of his forces invading their home planet of Salamandria as leverage, he gets them to betray the Turtles and lure them to his home planet of Sectoid 1 to capture them. After the plan works and Dregg reveals the Salamandrians' betrayal, despite learning from the Turtles that the Black Hole Generator pieces are now in the hands of the Triceratons, Dregg goes to speak to the Salamadrians in private. He double-crosses Mona and Sal Commander, having no intention of calling off his invasion of their home planet. After sending Leo, Raph, Mikey, and Casey to be prey for the Scorpinoid, he revels in his victory, before being convinced that Armaggon hit him on purpose out of disrespect thanks to April and her psychic powers. The distraction he gives them allows April, Donnie, and the Fugitoid to rescue their allies and escape before Dregg gives pursuit with dozens of Vreen and the Scorpinoid. However, when the Scopinoid strikes down Mona Lisa, Raph, fueled with fury, attacks Dregg head-on. Dregg is unable to overpower the grief-stricken Turtle, and his head is soon decapitated from his body, revealing a robot one underneath. Despite this revelation, Raph defeats Dregg, and the Ulixes clears out the Vreen and incapacitates the Scorpinoid, allowing the Turtles and their allies to escape Dregg once more.
Dregg manages to follow the Ulixes to the planet Magdomar as he wants revenge on the Turtles for killing the Scorpinoid, referring it as his favorite pet. After losing them again, Dregg teamed up with Mozar and offer him the location of the third piece of the Heart of Darkness, in exchange for the Turtles and 40 million Zemulaks (which he later extends to 100 million when he asks for refuge alongside the money in return for the last piece from Mozar). After getting the final piece and handing it to the Triceratons, Dregg was told that his money would be in a empty room. As he enters and sees no Zemulaks, it was revealed to be a trap as Dregg is locked in an airlock and Mozar sends Dregg into the freezing outside of space, presumably killing Dregg.
Dregg appears as part of Raphael's hallucinations induced by his fear of bugs while battling Stockman-Fly and his mutant flunkies. Thanks to advice from Master Splinter, Raphael is able to drive Dregg's image out of his mind and save his friends along with defeating Stockman-Fly's mutant lackeys.
It turns out that Dregg's presumed death by the Triceratons did not happen as Dregg survived to launch his original invasion of Salamandria. Though the Salamandrians fought him off, he swore to return. Later, he had managed to track Mona Lisa and Sal Commander all the way to the Turtles' home planet of Earth in his new living command ship, reveling in the fact he could now get his revenge on the Turtles and the Salamandrians by taking over Earth and using the human population for his own malicious intent. He also reunited with one of his best and loyal assassins, Newtralizer. As his ship laid hundreds of Vreen eggs to unleash Vreen all over New York City, he manages to capture Leonardo, Sal Commander, and later on, Donatello and Karai, while his Vreen captured the residents of Manhattan and cocooned them in the new hive they were making out of the Channel 6 building, as Dregg intended to turn the captive Terrans into living egg sacs for his Vreen army, even as Newtralizer suggested destroying the Earth outright. However, a joint effort by the Turtles using the Turtle Mech and the Earth Protection Force using their Utrom and commandeered Kraang equipment and weapons put Dregg on the defensive. Once Michelangelo freed his brothers, Karai, and Sal Commander, Mona attacked Dregg using a device given to them by the Utrom High Council, which appeared to affect Dregg as he couldn't stand being electrocuted by it. Raphael uses a severed power cord to electrocute Dregg so badly that it knocks him out cold, while Sal Commander knocks Newtralizer into the power core of Dregg's ship, setting off a chain reaction that threatened to destroy the whole ship. Mikey remained behind to buy the others time, while Dregg's ship attempted to flee back into space, but barely got airborne and gained some altitude before the power core overloaded and the ship was destroyed, presumably taking Dregg with it and ending his threat for good as he was still unconscious on the bridge when his ship exploded.
His appearance is that of a purple winged insectoid with four eyes, a mouth that is always frowning due to the design of his lips, a tail similar to a centipede's with pincers on the end, razor sharp fingers on detachable hands, and a very muscular build, able to easily overpower the Turtles, April, and Casey single-handedly during their first encounter and meeting. Due to his insect alien physiology, he also has a hive mind to allow him to command his Vreen drones, and if their connection to him is lost, they effectively stop fighting and flee without Dregg to give commands.
Lord Dregg is arrogant. Always believing himself to be superior to other races, he is quick to be angered by even the slightest incident, be it being bumped into, or having his latest purchase be destroyed by accident. He also boasts of his status as the ruler of Sectoid 1, and when provoked, proves to be a very tough enemy of those who cross his path. Lord Dregg is one to hold grudges and is rather vindictive as he persistently chased after the turtles through out space with ill-intent in revenge for disrespecting him, making him drop his expensive star spice and destroying his Vreen. Dregg is also deceitful and treacherous, as he underhandedly threatened to invade Mona Lisa and Sal Commander's homeworld unless they lured the Turtles to him, only to go back on his word after his plan worked. His hive mind allows him to control his Vreen drones, whom he dubs his "children," and is very sentimental if they are killed in combat right in front of his eyes.
- Armaggon - Armaggon was hired by Dregg to kill the Turtles after they offended him after their first encounter and to bring back their shells as proof that he succeeded. He would later tell Armaggon instead to bring back the Turtles alive so that he may personally torture them.
- Vrax Belebome - He was seen talking to Dregg about how he will give him the information about the pieces of the black hole generator and the Neutrino's will return soon with from Mikey's memories.
- Scorpinoid - Scorpinoid is Lord Dregg's pet. Dregg keeps him in a pit under his castle on Sectoid 1. He is Dregg's favorite pet and he loves him.
- K'Vathrak/The Newtralizer - K’Vathrak is an assassin who affiliates with Dregg on occasion.
- Xaxx Bees - Are drones that fall under Dregg's command.
- Ninja Turtles
- April O'Neil
- Casey Jones
- Y’Gythgba/Mona Lisa
- G'Throkka/Sal Commander
- Hamato Miwa
- Dregg's name is derived from the English word "dreg". This term refers to dirt and evil people.
- Lord Dregg in this series appears to take aspects of Maligna, the insectoid Queen of the Malignoids who was an enemy of the Mutanimals in the Archie comics.
- It was not yet revealed how he survived his presumed "death" as seen in The Ever Burning Fire.