In the compilation's version of Mega Man 8, some of the Robot Masters' voice clips play at incorrect pitches. In addition, the graphics of Mega Man walking away from Wily's Castle are absent from the credits sequence, as the developers were unable to port certain SNES graphical effects. In Mega Man 7, an instance of the word 'damn' was changed to 'darn' in order to retain an E rating. In Mega Man 6, the arranged music is incorrectly mastered and suffers from extensive peaking. Several of the NES games have remixed sound.

Some differences from the original games exist in a few cases. The Xbox version also includes the first episode of the Mega Man NT Warrior anime (based on Mega Man Battle Network game series) and the ability to change the control scheme. The PS2 version features the pilot episode of the Ruby-Spears Mega Man TV series, while the GameCube and Xbox versions feature the Mega Man episode of G4's Icons. There are also differences for the extras between each version. The PS2 and Xbox versions include some arranged music for the first six games, also originally present in the Complete Works versions. This mode adds helpers that provide game hints if the player is in need of help, revisions the appearance of the health and weapon energy meters and revisions the weapon subscreens for the first three games. The 'Navi Mode' present in the PlayStation ( Rockman Complete Works) re-releases of the first six Mega Man games is included in the Anniversary Collection versions as well.

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