In Devil May Cry and Devil May Cry 3, it must be unlocked by dying 3 times on Normal Mode, or in Devil May Cry by using a Vital Star on the first mission. This mode is only available from the start in Devil May Cry 4 and Devil May Cry 5. The player is allowed to keep items and abilities gained from each playthrough when moving to a higher difficulty, with the exception of Easy Automatic in Devil May Cry. Some games in the series feature cheats, DLC or other methods that allow the higher difficulty modes to be unlocked immediately, and starting out on a higher difficulty with a 'fresh character' is a common type of skill run for seasoned players. Typically, difficulties above the default will also alter enemy waves, having powerful enemies appear much sooner than they normally would.

In addition, enemy behavior is altered: lesser demons become more aggressive, bosses will utilize their special attacks more often, and in the highest mode enemies even gain their own Devil Trigger. Enemies have more Vitality and deal more damage, making the main character seem weaker. All games start the player on a 'normal' difficulty, but, after fulfilling certain criteria, the player can opt to play through the story missions again on a higher difficulty.