Set in modern times, in the fictional city of Vie de Marli on Dumary Island, the story centers on Dante and Lucia in their fight to stop a businessman named Arius from raising the demon Argosax and achieving supreme power. The story is told primarily through a mixture of cutscenes using the game's engine with several pre-rendered full motion videos.
- Matier - She is part of the clan of Vie de Marli. In her younger days, she and her clan fought against the demons alongside Sparda. Matier is cheerful and optimistic, and always seems sure of Dante's eventual victory. She is the one who guides Lucia to reunite the Arcanas and lure Dante to their island. At first, it is claimed that Matier is Lucia’s mother, but it is later revealed that Lucia was in fact created by Arius, who planned to dispose of her, until Matier found her and raised her as a daughter. In the end, she tells Lucia not to worry, and that Dante will eventually return from the demon world.
- Finis Demons - living cages resembling knights that come in three different types: the axe-wielding agofinis, the sword-wielding terreofinis and the mortfinis, which use shields with serrated edges that they fling at the player like yo-yos.
- Puia - annoying harpy-like demons that are hard to strike unless a ranged weapon is used.
- Mancer Demons - shrouded, ghost-like figures that come in three different types: pyromancers, who use fire magic, auromancers, who use wind magic, and brontmancers, who use lightning magic.
- Savage Golem - a creature that advances slowly and inexorably. When struck, pieces of it begin to disappear until only its legs are left, which then attempt to scurry away. If the legs are not destroyed, an entirely new monster grows from what survives. Its main attack is to suddenly grow long, deadly spikes that strike and then retract.
- Spicere - this demon resembles a cracked spiky meteor which, when the pulsating segments part, reveal an eyeball. When the player is close enough and seen by the eye, the creatures self-destructs.
- Erupt Gel - a jelly fish-like demon with a single eye only encountered in one of Lucia's missions.
- Orangguerra - A giant ape with glowing eyes that has an attack powerful enough to send Dante flying. It also can grab the ceiling and swing from it. In close proximity, it is quite dangerous, as it can squeeze a significant amount of life energy out of Dante with its huge hands.
- Jokatgulm - A poisonous blue octopus-like boss whose head must be attacked. Blocking the head are her tentacles, which must be destroyed to advance. However, if the player waits too long, the tentacles regenerate and must be destroyed again.
- Infested Chopper - a boss that looks like a charred helicopter with a monstrous eye attached to its side, the Infested Chopper shoots and fires homing missiles at the player. When it takes enough damage, it moves to another part of the city. The player must then track it down and begin the battle anew, making this fight, preceded by three much easier Infested Tanks, somewhat difficult.
- Bolverk - A skeletal demon warrior who fights with an extendable spear and an aura of darkness, and his single eye possesses both knowledge and hate. He is served by Freki & Geri, two wolf-like demons reincarnated from Bolverk's old allies. Dante first battles his wolves before facing their undead master who still holds a grudge against his father and Bolverk's old enemy, Sparda.
- Nefasturris/Nefascapitas - A monsterous titan (Nefasturris) come to life from a skyscraper, the upper half of its body attacks Dante by shooting lasers and balls of energy from its mouth. After taking enough damage, the giant's head (Nefascapitas) comes loose and comes after the devil hunter. This is the more difficult part of the battle, since the mouth fires projectiles at an increased rate combined with summoning waves of lasers from different angles that must be avoided.
- Tateobesu - A giant demon fish that has the ability to render itself invisible.
- Furiataurus - It wields a massive hammer, and its body is made of hardened lava and flame in the shape of a minotaur.
- Trismagia - An ancient and powerful demon who is the oracle of the netherworld. He looks like an enormous head with three faces and three sets of eyes representing his ability to use the elements of Ice, Fire, and Electricity. He has the ability to split into three heads which can attack one at a time, or recombine them for a powerful strike using all three elements.
- Demonochorus - living cherub statues that dart about, glowing with an eerie blue light. They cast sinister spells that deplete the player's health, but are relatively weak enemies.
- Infestants - bug-like demons that have long thin bodies and many legs that are constantly looking for a host.
- Secretaries - Really nothing more than mannequin-like demons enchanted into believing they are living beings, the Secretaries are the personal bodyguards of Arius. They bear an eerie similarity to Lucia.
Devil May Cry 2 is an action game where the player guides either Dante or Lucia through an urban environment, fighting groups of demons in fast-paced combat. The game itself consists of missions with specific goals in the play area of the game itself. Like the first Devil May Cry, the player's performance in each mission is ranked from D (poor/Don't Worry) to S (excellent/Showtime) based on the time taken to complete the mission, the amount of Red Orbs collected, the overall "style" displayed during fights which occurred, item usage, and damage taken. In contrast to the rest of the gameplay, the style judging system used in the game has been cited as being the most harsh in terms of how it judges the player's performance.
Combat itself is based on the "style" the player demonstrates during a fight. The rating the player gains for style is improved by hitting enemies continuously while avoiding damage. This ranges from "Don't Worry", progressing to "Come On!", "Bingo", "Are You Ready?" and peaking at "Showtime". If the character takes damage, the style rating falls to "Don't Worry".
The game's controls are simple, converting short sequences of button presses into complex on-screen actions. New to the series is an evasion button, which allows Dante or Lucia to roll, dodge enemy attacks, or run along walls. Another new feature is a weapon-change button, which allows the player to cycle through ranged weapons without switching to the inventory screen.
The game also features puzzle-solving and exploration elements. Gameplay involves the player examining their surroundings to find items and orbs. Red Orbs are used to acquire new combat powers and abilities for the characters. These Red Orbs are "the blood of demons"; enemies drop them when they are defeated. Dante and Lucia can also opt to instead purchase items, which allow them to restore their damaged health or even instantly revive should they be killed by an enemy's attack.
The Devil Trigger ability enables Dante and Lucia to transform into a devil form. This changes their appearance, increases their strength and defense, slowly restores health, and enables them to use special attacks. The Devil Trigger state lasts as long as there is power in the Devil Trigger Gauge, which increases by attacking or taunting enemies in the normal state and decreases by attacking in the Devil Trigger state or using Devil Trigger-only attacks. Unique to this game is the Desperation Devil Trigger — an enhanced form of the Devil Trigger — available to Dante when he is low on health.
Devil May Cry 2 begins with Lucia and Dante separately entering a museum where an important item called the Medaglia is stored. After defeating a group of demons in the museum, Lucia invites Dante to follow her to the Dumary Island, where he is introduced to Matier, her mother. Matier explains that she once fought alongside Dante's father, Sparda, to defend the island against demons. She asks Dante to help fight Arius, an international businessman who uses demonic power and seeks to conquer the world. Dante flips a coin in answer, and decides to help when the coin lands on heads. After Dante leaves Matier and Lucia discuss the Arcana, the items required for Arius to raise Argosax, a wicked and powerful king who ruled the Demon World.
Lucia eventually confronts Arius, who reveals that she was his creation. When Lucia moves to strike Arius, he uses his magic to blast her away. Shortly afterward, Dante meets up with Lucia, who gives him the last of the Arcana before leaving. Dante then encounters Matier and tries to pass the Arcana to her. Matier, in turn, asks Dante to take the Arcana to save Lucia, who has gone to fight Arius again. Dante flips the coin again to decide if he will help; it lands on heads, and he departs to aid Lucia. Meanwhile, Lucia enters the Uroboros tower and attacks Arius, who captures her. Dante arrives and trades the Arcana for Lucia, then attacks Arius. To escape, Arius forces Dante to decide between saving Lucia or killing him.
Lucia, worried about the ritual and conflicted about herself, wonders how they will stop Arius. Dante waves her off, stating he will find a way. Dante leaves Lucia to think as he departs to defeat Arius. Matier arrives a short time later, sets Lucia's mind at ease, and decides to rejoin the fight against Arius. Dante arrives to find Arius in the middle of his immortality-inducing ritual. Apparently not at all fazed by the completion of the ceremony, Dante stands confident. Another fight ensues, in which Dante finishes Arius off with his pistols. Outside, Lucia confronts Dante and demands that he kill her because she fears she will become a demon herself. Before the issue can be resolved, a large stream of energy strikes the tower and a portal to the demon world is opened. Dante and Lucia argue over who will enter and close it from the inside; Dante offers to leave the issue up to fate. He flips the coin and it once again lands on heads, leaving Dante to enter the portal to deal with Argosax after leaving the coin with Lucia.
After Dante departs, Arius returns to life bearing demonic power. While Lucia fights Arius, he finds himself injured and attempts to distract her, a tactic which fails; Lucia goes on to defeat him. Within the portal, Dante fights and defeats the partially summoned Argosax. Finding the portal closed, Dante instead drives further into the demon realm on a motorcycle. In the aftermath of the battle, Matier attempts to reassure Lucia about Dante's fate, insisting that Sparda returned from a similar trip. Lucia examines the coin Dante left with her and discovers that both sides are identical. Sometime later in Dante's shop, Lucia muses about Dante. Outside the sound of a motorcycle echoes, and Lucia leaves to investigate. It is left up to the player's interpretation if this is Dante or not.
Despite the success of the original Devil May Cry, the sequel was not created by Hideki Kamiya or Capcom Production Studio 4. The first notice Kamiya's team was given about any sort of sequel occurred during localization of Devil May Cry in North America and Europe, a move which greatly surprised Kamiya. Since the game's release, Kamiya has expressed disappointment that he was not called on by his superiors at Capcom to direct Devil May Cry 2.
Instead, the sequel was granted to Capcom Production Studio 1 and Hideaki Itsuno, the team responsible for Capcom vs. SNK 2. According to producer Tsuyoshi Tanaka, the thrust of the design was to make Devil May Cry 2 bigger than its predecessor; Tanaka estimated that the game's environments were approximately nine times as large as the first. The emphasis on puzzles was also downplayed, with the camera system revamped to allow for better action scenes. Changes from the first game were influenced by surveys distributed by the development team, allowing them to patch any areas identified as weak by the people surveyed.