While the Legion is focused primarily on world peace-keeping, they often come across meta-humans of evil intent, mobs, and even aliens. These are their enemies ranks.

The primary threat is Matrix Prime, an alien from the planet Kronon. He has the power to technologically reform any organic matter, use energy bolts, and siphon off energy. He is cold, ruthless, has no regard for anything organic, and is the most intelligent being in existence. His first and only encounter with the Legion resulted in what was later called the Great War. Thousands of his soldiers, Mandroids, were deployed and began to capture humans for their biological component. The Legion fought his forces for thirteen days before launching a full-out assault on Matrix's compound, and destroying him.

Matrix's soldiers are referred to as Mandroids, due to the fact that they need a biological component to survive. They bond humans to their central processers, turning them into cyborgs. Upon Matrix's defeat, all of them were destroyed, and the humans rescued.

The second threat is Mr. E, aka Jonathan Blake. This is the version of Hunter from universe 287036. He has increased strength, stamina, durability, agility, healing himself, and growing finger blades. He is the ruler of the world in his universe, after killing his own version of the Legion, known as the Armada. He is a crime boss in this universe, and whenever an opportunity for business comes up, he jumps at the chance.

Another threat is Hypothermia, aka Brianna Jefferson. She has cryo-kinesis, the ability to create ice, manipulate cold, etc. She is a psychotic, feminist, blood-loving killer. And she loves nothing more than to ice her victims. However, due to complications with her Meta-Gene, she can not remain in an environment that isn't below freezing. She uses a high-tech containment suit consistently flowing with liquid nitrogen in order to survive. She and Maniac have formed a friendship during their incarceration. Recently, though, she has received genetic experiments that allow her to survive outside of her survival suit permanently.

Another threat is Maniac, aka Julie Devros. She was a patient at an insane asylum, and she developed her powers during a freak accident in a cognitive-recalibration device. She can instill madness upon anyone just by establishing eye contact with them. She is, in a word, crazy. And she will not stop until everyone is mad like her. She and Hypothermia have formed a friendship during their incarceration. However, upon Codex revealing her identity to her, she remembered her past and was cured of Maniac. Julie is currently receiving psychotherapy to make sure Maniac is gone.

The final threat was Captain Damage, aka Hector Rosenblatt, age 12. He had no powers, and could be taken out with a soft punch. He was a kid in a costume until he uncovered a Mandroid suit. Reprogramming the suit, he bonded to it's central processor to become DamageDroid, a cyborg who could form plasma weaponry and mimic meta-human abilities. Then, both merged their bodies to form one single entity, and became Eliminator.

Although these are the main threats to the Legion given the many times they attack, they are several other enemies, most of them groups.

The first group is the Blackjack Brotherhood. They are comprised of several mob bosses and corrupt city officials. They include Ace of all suits, King of Spades, Queen of Hearts, Jack of Clubs, and 10 of Diamonds. Although they don't wear costumes, and escape arrest constantly, they are still known as the criminals they are.

The next group threat is the Serpent Sisterhood. Consisting of only female mutations that have been enhanced to exhibit snake-like abilities and venomous fangs, they are considered highly dangerous. They are lead by Queen Cobra, who sees men as an oppressive, weak, and pathetic life form. The venom they inject causes burning sensations, depth perception loss, loss of vision, hallucinations, and even death. Even though Medic's healing powers takes the danger of death away, the venom still needs time to exit the victim's blood-stream.

The only supernatural threats are the Demon Guild. The first member is the Hessian mercenary known as the Headless Horseman. He wears a black robe and silver armor, wields a 2.5 foot sword, and rides a black horse with a flaming main and tall. The second is the demon known only as the Assassin. He is the combination of the Apocalypse Horseman of Death and War. He wears a black combat outfit with Kevlar, and has skin made of flowing blood, and only two black sockets for his eyes. The third is a mummified version of Set, the Egyptian god of evil. He is able to manipulate darkness, and upon skin contact, can drain a person's life. Last among them is Dracus, the dark force more commonly known as Dracula. He is a living shadow, forged from death itself, and feeds off a person's very life-force. The four of them serve a master that nobody ever sees, and they refer to it as "the Dragon", suggesting they may work for the Devil.

Another group is the four vigilantes known as the Death Penalties. The leader is the Hangman, whose great strength helps him to lift his victims off the ground in a noose. Next, is Electric Chair, who uses electrical abilities to negate brain bio-electricity. Next is Lethal Injection, whose fingers have been replaced with syringes, each filled with a different poison. Last is Gas Chamber, whose gaseous body allows him to enter a person's lungs and suffocate them. Although they are murderers, their only targets are low-level criminals who have been released from jail for felonies. They take it upon themselves to finish what the law started. Even though they claim to be heroes, ridding the world of criminals, they still disobey the law, and the Legion has no choice but to stop them.

The final group threat is the E. Nigmas. The are the henchmen of Mr. E, and all of them are highly trained assassins. They serve his every order, and they commit suicide when captured. The leader of the E. Nigmas is the costumed man known as Predator. He is a dark reflection of both Mr. E and Hunter.

Most, if not all, of the Legion's enemies who've been arrested have been sent to BloodGate Prison. This is the only facility on Earth that is equipped to safely detain and contain meta-humans. It has walls that can survive a nuclear attack, prison jumpsuits that can electrocute an inmate if needed. The cells floors are flooded with motion sensors that track every movement the inmates make, as well as blast doors capable of surviving ten tanks, and locks that only open with a Legion member's D.N.A. The escape-to-arrest ratio is 7 to 15, and the parole number is zero.

However, there is one opponent that was never imprisoned, captured, or even defeated for that matter. The final threat is the assassin known as the Operative. He is a cyborg, with 75% of his body replaced by bionic implants. He wears a white flag on his shoulder, to show that he belongs to no one country or employer. He has strength, speed, durability, invulnerability, and resistence to both EMP blasts and magnetism. He uses his skills and robot implants to beat his opponents to the point of pyhsical exhaustion, where it even hurts to breathe. He appeared in the US only once, as part of a hit on the Legion, and has appeared throughout the world for over 2,000 years. Due to his historical significance, he has become part of myths and legends throughout all world cultures.

However, a small group of criminal was recruited by the government to be a top-secret task force in high-risk operations. They serve for four years and are then given parole. They're referred to as the Infiltrators. They consist of several criminals who all have a specific purpose. The leader is Sargent Bullet, a U.S. soldier who takes high risks. Next is Eliminator, who serves as the team's gadget man. Next is Hypothermia, serving as a climate manipulator. Next is E. Nigma #2, who serves as the team's strategist. Next is 10 of Diamonds, who offers resources and funding. Last is Julie Devros, formerly Maniac, who serves as the combat expert. They all serve with explosive nano-bots in their bloodstreams, ensuring they don't run or try anything stupid.