The chronological order of the Devil May Cry series does not follow the release order of the games. The first game in the time line is Devil May Cry 3, followed by Devil May Cry, then "Devil May Cry the Animation" then Devil May Cry 4, and finally Devil May Cry 2.

The plot of the series begins with Devil May Cry 3 in Dante's as-of-yet unnamed shop as a mysterious man named Arkham appears to offer an invitation from Dante's brother, Vergil. An immense tower erupts from the ground a short distance away from the shop and Dante takes the situation as a challenge. Following numerous battles Dante arrives at the tower's summit, Temen-Ni-Gru, and battles Vergil. Vergil defeats Dante and departs. He eventually catches up in the control room located in the tower's basement. The brothers battle again until they are interrupted by Lady, then Arkham, who has been manipulating them all to reactivate the tower. Arkham intends to steal the Force Edge, Sparda's sword.

Dante crosses over to the demon world and catches up with Arkham, and he and Vergil work together to bring down Arkham. Dante and Vergil battle, and Dante is victorious. 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".

Devil May Cry begins with Dante being attacked in his office by Trish. He brushes off her assault and she claims that the demon emperor Mundus is planning a return. Dante explores Mallet Island, encountering a variety of demons, including one named Nelo Angelo. Dante is defeated but Nelo Angelo flees. Other encounters with Mundus' demon generals serve to indicate Dante has become even more powerful than his father since his initial awakening in Devil May Cry 3. Nelo Angelo attacks twice more in later missions, and is eventually revealed to be Dante's twin brother, Vergil. Dante enters the underworld in search of Mundus, where Trish sacrifices herself to save him. Dante releases the power of Sparda that Vergil sought in Devil May Cry 3. Dante and Mundus then battle on another plane of existence. Trish returns and lends Dante her power. Dante then defeats Mundus. Dante and Trish escape as the island collapses, and later work together in the renamed shop, "Devil Never Cry".

Devil May Cry: The Animated Series is an anime series that led up to Devil May Cry 4 and tells more about Dante, Lady, and Trish's adventures.