Speculation has risen among fans that Serges is actually the mind of Dr. Wily transferred into a Reploid body. Some dialogue from the Japanese version has him talk about Dr. Light, X's creator, and his appearance and his tendency to rely on machines for transport and attacking resembles Dr. Wily in many ways. Keiji Inafune has never confirmed or denied the fact, and has seemed reluctant to do so, suggesting the theory could be true.

The conception of both Sigma and the X-Hunters have similar origins. Keiji Inafune originally had designs for a team of three villains, borrowing elements from all three designs to eventually make Sigma for the first game. The designs of those three characters were then later reworked to be the X-Hunters of Mega Man X2.

Due to the limitations the developers were experimenting with, both Violen's second form (to match the new forms of Serges and Agile) and a fourth female X-hunter had to be removed. At the time they would have been called the "Four Guardians".

This game, just like the last, has a secret Street Fighter move that you can unlock if you get every collectible in the game. In the second Sigma stage, once you get to a fork where you can go up or down a ladder, use your ice shot to freeze the bat and climb up the ladder at the top. Pass the obstacles, and when you are falling down, hang to the left. If you make it without losing energy (you can use an energy tank), there should be a Dr. Light capsule that will teach you the Shoryuken.

Holding down the B button on Controller 2 while turning on the SNES will display a diagnostic screen for the Cx4 chip included in the cartridge. This chip is responsible for the trigonometric calculations necessary to display the animated wireframes in the game.

If the game is finished without getting the armor parts, Zero will make a cameo in the ending credits.

The sky in Wheel Gator's stage will turn from day to night on its own over a long period of time. This is noted by distinct color changes in the sky and by the lights in the city buildings getting brighter the darker it gets.