An enhanced version with the subtitle Anniversary Edition was released for Android and iOS in August 2020, for Nintendo Switch in November 2021, and for Microsoft Windows and Xbox One May 2022.

Kodaka aimed to develop a unique plot to give players more mysterious elements in a group of islands, inspired by the television series Lost.

However, the gameplay elements involving class trials earned mixed responses; some writers found some parts of the game uninteresting, while early ones proved unchallenging.

A loose sequel to the series, called Danganronpa V3: Killing Harmony, with similar gameplay but a different storyline was released on January 12, 2017.

Class Trials, which uses the first-person shooter genre, mostly consist of Nonstop Debates, in which players must find weaknesses in the students' discussions and shoot them with "Truth Bullets" that contradict them.

Controls from the last game are slightly revised; players must spell out a phrase in the correct order at the end of the section rather than firing a specific Truth Bullet.

In the Closing Argument, players fill in a comic strip depicting the events of a crime; panels are selected from stocks, and must be chosen correctly, rather than being available from the start.

In these sections, players must slash apart their opponents' argument to gain dominance in the conversation and reveal new information before using a "Truth Blade" to strike the correct weak point when it appears.

Magical Girl Miracle☆Monomi is a minigame in which players control Monomi, a mentor of the main characters, who fights waves of monsters.

[8][6] In Goodbye Despair, players control the new protagonist Hajime Hinata, an amnesiac boy who has just become one of Hope's Peak Academy's "Ultimate" students alongside fifteen others, including the calm but mentally unstable Lucky Student Nagito Komaeda and the seemingly ordinary and quiet Gamer Chiaki Nanami.

However, the school's principal Monokuma hijacks the trip and usurps Usami’s authority, reducing her to a powerless mascot named Monomi.

If the students can identify a murderer in a Class Trial and vote accordingly, that culprit is executed, but if they make the wrong assumption the killer goes free whilst everyone else is sentenced to death.

The Affluent Progeny Byakuya Togami (later revealed to be the Ultimate Impostor) is inadvertently killed by Chef Teruteru Hanamura in an attempt to stop Nagito from committing the first murder.

Musician Ibuki Mioda and traditional dancer Hiyoko Saionji are killed by nurse Mikan Tsumiki as she is under the effects of Despair Disease.

Team Manager Nekomaru Nidai is killed by animal breeder Gundham Tanaka in an honorable duel to prevent the rest of the students from starving to death.

During the graduation, it is learned that she is actually an AI program created by the late Chihiro Fujisaki to observe and protect the students during the Future Foundation's experiment.

After Chiaki's death, Hajime recovers a memory of arriving at the islands with Nagito, who had transplanted the arm of a woman, Junko Enoshima.

The other students hesitate, afraid of reverting to their original personalities, but with the help and encouragement of Chiaki's essence, Hajime awakens to his true talent as the Ultimate Hope.

As a result, writer Kazutaka Kodaka was attracted to the idea of creating the novel Danganronpa Zero, which he decided to write after consulting producer Terasawa.

Kodaka felt the second half of Goodbye Despair did a better job of making the characters real than Trigger Happy Havoc.

Kodaka also said the islands were used to give players more content to explore, comparing the sequel to the television series Lost in terms of amount of plot twists and how different the narrative is.

A limited edition that included a Monokuma PSP pouch, an art booklet, a soundtrack and audio commentary CD, keychains and badges, and a download code for a custom theme was available.

[21][22][23] Localization member Robert Schiotis said finding a voice actor for Nagito in the English-language version proved challenging because he is meant to clash with Makoto's ideals.

[27] An enhanced version for Android and iOS, under the name Danganronpa 2: Goodbye Despair Anniversary Edition, was released on August 20, 2020.

[40] GameSpot enjoyed the class trials for staying true to the original formula but gave a negative response to the minigames, which the reviewer said feel unnecessary.

[36] GameRevolution said the additions to the original class trial system are enjoyable because they provide more variety in terms of gameplay but found some mechanics annoying.

Video Gamer praised the returning villain Monokuma and said the cast provide enjoyment despite having mixed thoughts about their originality due to most being stereotypes previously seen in other games.

[41] Joystiq praised the balance between lighthearted moments and violent deaths, and said the characters are likable and distinct enough from each other enough to make their dating sim events enjoyable and easy.

[46] Similarly, Polygon found few character bondings in the game worthwhile due to some being less likable than the original Danganronpa and the rest dying across the title.

Dark Horse Comics has released the Chō-Kōkō-Kyū no Kōun to Kibō to Zetsubō manga under the title Danganronpa 2: Ultimate Luck and Hope and Despair in North America on September 15, 2018.