Dante's Inferno is an action-packed journey through the world of Inferno, based on the first canticle of Divine Comedy by Dante Alighieri. In this adaptation Dante is re-imagined as a templar knight, a veteran of the crusades, who comes home to discover his beloved Beatrice has been killed. At that moment the murderer stabs Dante in the back as well. Dante is however able to resist Death, who wants to take him down to hell, and robs him of his scythe. With these new powers he can descend into the inferno by himself to track Beatrice whose soul has been captured by the devil. Lucifer plans to marry her soul, which should have gone to the heavens instead, to flee from hell and overthrow God. To prevent this from happening Dante has to travel through the nine circles of hell and master their demons to finally undergo his toughest test. Matching the original Inferno theme of recognizing and rejecting sin, he has to face his own past, his own crimes and his own sins to free Beatrice. Through the journey he often meets the poet Virgil who explains the different circles and drawn flashbacks show how Dante sinned in each circle during the crusades.

The gameplay is largely similar to the God of War games. Dante's preferred weapon is a scythe and he commands magic through a holy cross he carries which has been given to him by his beloved Beatrice shortly before her death. This magic utensil sends out rays of light that kills all evil it touches. Dante even can tame some demonic beasts and use these to his own needs. Players however have to choose between a holy and an unholy path. When grabbing enemies or encountering trapped characters (including a large number of historical figures) Dante can choose to punish or absolve them. Either choice is rewarded with unholy and holy experience points respectively. This allows Dante to level up in one of the two tech trees and spent the souls he has collected there. It is not possible to max out both sides, so a certain path needs to be chosen. The unholy side focuses on the powers of the scythe while the holy side focuses on the cross.

With each level new abilities can be purchased. For the unholy path most of these are centered around stronger scythe attacks, while the holy path focuses on the ranged abilities of the cross. There are also general abilities such as expanding the health or mana meter, extending the redemption meter, or providing additional defence against attacks. Dante has multiple combo attacks, he can dodge, block and revenge, attack from the air, grab and throw enemies, and perform acrobatic stunts such as sliding down large spines, hanging and swinging from ropes, or clinging to specific walls. These stunts are often used to solve minor environmental puzzles. Fighting enemies also fills up a redemption meter, which can be activated when it is maxed out, granting faster movement and attacking speed. During his journey he will also master four strong forms of magic, also enhanced through the tech tree and those depend on a separate mana meter to execute. The currency to buy new abilities is souls of the enemies he defeats. Souls are gathered automatically when killing enemies, and both health and mana is largely replenished through shrines. Many large battles feature quick time events (QTEs) where the player needs to press the correct buttons when prompted, to defeat a large enemy. These also appear as a mini-game when you need to absolve souls of major characters.

A final way to extend his abilities is through relics. These are collected throughout the journey and are fitted in a limited amount of slots (initially two). These provide additional assistance such as resisting magic, making attacks stronger or regenerate health and mana. By equipping them the relics can level up two times to render them more effective. Since the amount of slots is limited they often need to be switched according to the situation.