Quick Man is a combat Robot Master created by Dr. Wily using Elec Man's design as a base. Quick Man is made of lightweight materials, allowing him to move at very high speeds. Though his top running speed is unknown, Quick Man is one of the fastest Robot Masters in the Mega Man series possessing a standard cruising speed of Mach 5. His weapon is the Quick Boomerang, small boomerang cutters that he can shoot from his right arm. Because of a defect, Quick Man is vulnerable to Flash Man's Time Stopper. Quick Man and Turbo Man are also rivals. His level in Mega Man 2 contains a number of deadly lasers known as Force Beams.

Metal Man was the first Robot Master built by Dr. Wily, created specially for combat for his revenge against Mega Man. Wily based Metal Man's design on Cut Man. His weapon is the Metal Blade, several large saw blades made of ceramic titanium that he can throw at high speed. Because of a design flaw, Metal Man is vulnerable to Mega Man's Mega Buster. When Dr. Light saw Metal Man for the first time, he commented that he's "the dentist of the future".

Flash Man is a Robot Master created by Doctor Albert Wily. In combat, Flash Man can stop time to attack opponents while they cannot move with the rapid-firing blaster in his right arm. To his enemies, it appears Flash Man is moving at light speed or teleporting. It is believed that this ability is a perfected form of what the Robot Master, Time Man, was capable of. However, unlike Time Man, who could only slow down time with Time Slow, Flash Man can stop it completely with Time Stopper.

Air Man is a Robot Master created by Dr. Wily specially for combat. Air Man has his face in his torso instead of a head, a design said to be intimidating. Air Man can generate powerful winds with the propeller in his torso to pull or push enemies, and can attack with small tornadoes with his Air Shooter. Air Man dislikes Fall season because the leaves get stuck in his fan, the reason he is weak to Leaf Shield.

Crash Man, known as Clashman in Japan, is a combat Robot Master that was built by Dr. Wily using the designs of Bomb Man and Guts Man as a base, having explosive weapons and a thick armor that can withstand explosions. He also has high speed and agility. His main weapon is Crash Bomber, a powerful time bomb with a drill that attaches itself to the target.

Wood Man   is a combat Robot Master created by Doctor Albert Wily using a special coating material obtained from natural cypresses, his body being made almost completely out of wood, including some of his mechanisms. Because of this, Wood Man has great physical strength and resistance against physical blows, but is somewhat slow, and highly vulnerable to fire and cutting weaponry.

His weapon is the Leaf Shield, leaf-shaped electromagnetic pieces of metal, sharpened around the edges, that can be used to protect himself and attack enemies in different ways, including launching them in rings of four or eight, and summoning them down from the ceiling to fall down onto the player. Due to his flammable construction, his primary weakness is the Atomic Fire.

When the Mecha Dragon appears, it will chase Mega Man breaking the platforms along the way, and at the end of the path battle will commence. It hovers on the left side of the screen shooting fireballs, and touching him is lethal. One strategy when facing it, is to stand on the top block to avoid falling into the pit and use Quick Boomerang. Another and somewhat safer method, is to use the Mega Buster since it inflicts the same amount of damage and allows the player to keep their distance.

PicoPico Master, is the boss of the second Wily stage of Mega Man 2. It is a guard system room with blocks that form into mini-robots, that was originally created by Dr. Light to protect his home. When Dr. Wily saw their effectiveness, he added a modified version of them to his fortress. They attack by simply flying toward Mega Man. When fourteen of these enemies are defeated, the room simply shuts down. Bubble Lead can defeat the robots in one hit, but as it may be difficult to hit them with it, it is recommended to use Metal Blade instead. As more of them are destroyed, the remaining ones will begin moving around the room faster.

Guts-Dozer, is the boss from the third Wily Castle stage in Mega Man 2. He is a large tank based on Guts Man's design, that looks like a giant Guts Man with spiked shoulders and caterpillar tracks instead of legs. He releases projectiles from his mouth, and Mets exit from the opening on his chest. Mega Man can stand on his treads to reach his head, the only part of his body that receives damage.

Boobeam Trap is the boss of the fourth Wily stage from Mega Man 2, a resistant protection system. The room has five flashing beam guns in the walls that fire simultaneously at intervals, indicating they will fire when they flash faster. They can only be destroyed with the Crash Bomber. The room also has some Destructible Blocks protecting beam guns.

First form: Wily Machine 2 goes back and forth using energy shots that go down and rise in an arch to the top of the screen. It is very weak to Atomic Fire, being defeated with two fully charged shots or less, depending on the difficulty. If the player used Atomic Fire on Wood Man and there is no energy left for a charged shot, it is recommended to use Crash Bomber or Metal Blade. When all of its health is depleted, the front part of the machine will blow up and Wily will appear.

Second form: Damaged, the Wily Machine 2 now shoots multiple bouncing balls that are difficult to avoid. This form is now immune to Atomic Fire, but is still vulnerable to Crash Bomber (and can be destroyed with a single Crash Bomb explosion if it is aimed and timed properly), but since the player is most likely going to be low or out of Crash Bomber from the previous fight, it is best to use Metal Blades or Air Shooter. The player should use his weaknesses to defeat him quickly and use E-Tanks if necessary. After destroying the Wily Machine, the floor will blow up with the Wily Machine and the player will fall to the last level, leading to the final battle against the Alien.