The plot begins with Devil May Cry 3 in Dante's as yet unnamed shop as a mysterious man named Arkham arrives with a message from Dante's brother, Vergil.^[13] An immense tower erupts from the ground a short distance away from the shop, and Dante takes it to represent a challenge from Vergil.^[14] Following numerous battles Dante arrives at the tower's summit, Temen-Ni-Gru, and battles Vergil. Vergil defeats Dante, apparently killing him, and departs the summit. However, the dormant devil power within Dante revives him, and he sets out in pursuit of Vergil. He eventually catches up to him in the control room located in the tower's basement. The brothers battle again until they are interrupted by Lady, then Arkham, who reveals that he has been manipulating all three of them to reactivate the tower. He intends to steal the Force Edge, Sparda's sword, and reopen the gates to the demon world, over which he will rule.^[15][16] Arkham leaves Dante, Vergil and Lady for dead and heads into the demon world. However, Dante follows him, eventually catching up with him, where he and Vergil work together to defeat him. Dante and Vergil then fight one last time, with Dante proving victorious. At this point, Vergil then dives deeper into the demon world. Returning to the human world, Dante meets Lady outside the tower where she coins the phrase "devil may cry" while trying to comfort Dante over the loss of his brother. They form a friendship and the beginnings of a partnership in demon-slaying, and he names his shop "Devil May Cry".^[17][18]
Devil May Cry begins with Dante being attacked in his office by Trish. He brushes off her assault and she explains that the attack was simply a test to see if he really is the son of Sparda, as the demon emperor Mundus is planning a return, and only a descendent of Sparda can defeat him.^[19] Dante explores Mallet Island, where Mundus is set to return, encountering a variety of demons, including a strangely honourable opponent named Nelo Angelo.^[20] Dante is defeated by Angelo, but upon Angelo seeing Dante's locket, with a picture of his mother, he flees, sparing Dante's life. Other encounters with Mundus' demon generals serve to indicate Dante has become even more powerful than his father since his initial awakening on the summit of the tower in Devil May Cry 3.^[21] Nelo Angelo attacks twice more in later missions, and is eventually revealed to be Dante's brother, Vergil, who has been forced into Mundus' service since diving into the demon world at the end of Devil May Cry 3. Dante defeats Angelo, killing him, and releasing his brother from Mundus' control. He then enters the underworld in search of Mundus himself. Once there, Trish sacrifices herself to save him, and Dante comes to understand the power of Sparda that Vergil had sought in Devil May Cry 3.^[22] Dante and Mundus then battle on another plane of existence, and Trish returns, lending Dante her power, and helping him to defeat Mundus.^[23] Dante and Trish escape as the island collapses, and later work together in the renamed shop, "Devil Never Cry".
In the Devil May Cry: The Animated Series, Dante is hired as the bodyguard of a young girl named Patty. While initially skeptical of his personality, Patty winds up growing attached to Dante and spends most of her time at his shop, often cleaning it or decorating it in a "girly fashion", much to Dante's dismay. While Dante's main job during the series is to protect Patty, he spends most of his time doing odd jobs he receives at his shop (which has been renamed back to "Devil May Cry" sometime after the events of Devil May Cry). Lady appears, working as an independent Devil Hunter, to hire Dante in order to pay off a huge debt Dante owes. Trish also returns, and it's revealed that she has been working away from Dante for some time in order to try to establish a solo career as a Devil Hunter. Lady and Trish meet for the first time and do not get along right away. Despite this, the three wind up working together to take on certain difficult jobs. Near the end of the series it is revealed that Patty's mother is the descendant of a human sorcerer, who once sealed away the power of an ancient devil lord, Abigail. Eventually the demon Sid emerges as the villain of the series, and reveals his evil plot involving the sealed away power of Abigail. While Lady and Trish fight off demons summoned by Sid, Dante fights and kills Sid himself. Sometime later, Dante, Trish, and Lady all get hired on the same job and take bets on who will win. Patty comes into Dante's shop to clean, showing that the two continue to have a somewhat father-daughter type of relationship.
Devil May Cry 4 follows young demon hunter Nero from the Order of the Sword who awakens his own demonic powers while facing Dante after he had killed his leader. Nero goes on a quest to capture Dante but learns the Order is also causing the appearance of several demons. The Order learn that Nero has Sparda's blood in his body and the leader Sanctus captures by using his girlfriend as a bait. Dante decides to save Nero first by defeating the demon summoned by the Order of the Sword and then by giving him the sword of his brother, Yamato. After Nero awakens, he finishes off Sanctus and befriends Dante who lets him retain Yamato.
Devil May Cry 2 begins with Dante meeting an associate, Lucia, in a museum. She invites him to Dumary Island, where he meets her mother, Matier. She asks for his help in fighting Arius, a businessman who wields demonic power and is planning to use a collection of magic artifacts, the Arcana, to call forth a devil lord known as Argosax.^[24] Dante flips a coin, and based on the result, he decides to help.^[25] Lucia confronts Arius, who reveals that she was his creation.^[26] Shortly afterward, Lucia gives Dante the last of the Arcana before leaving to face Arius alone.^[27] Dante then encounters Matier who asks Dante to take the Arcana to save Lucia from Arius.^[28] Lucia attacks Arius, though he captures her. Dante arrives and trades the Arcana for Lucia, then attacks Arius, who escapes.^[29] A large stream of energy strikes the Ouroboros tower and a portal to the demon world is opened. Dante and Lucia argue over who will enter, but Dante flips his coin to determine that he will be the one to go.^[30] After Dante departs, Arius returns to the human world, though Lucia goes on to defeat him.^[31] Within the portal, Dante fights and defeats the partially summoned Argosax. Finding the portal closed behind him, Dante instead drives further into the demon realm on a motorcycle. In the aftermath of the battle, Matier insists to Lucia that Sparda returned from a similar trip. Sometime later in Dante's shop, Lucia muses about Dante and examines the coin he gave her, discovering it is two-headed. Outside the sound of a motorcycle echoes, and Lucia leaves to investigate. The player is not shown whether or not it is Dante.