Production of Dead Cells began after Motion Twin planned development for a follow-up to their previous browser game Die2Nite.

They took inspiration from the Engineer character class from Team Fortress 2, and remade Dead Cells into an action platform game where the player would utilize a variety of combinations of weapons and skills.

[10] As they explore a series of levels and fight the creatures within, the player can collect an in-game currency called Cells from defeated foes.

Cells can be used to purchase permanent upgrades, such as potions that restore hit points or additional weapons that may be randomly obtained during a playthrough.

[12] Levels are procedurally generated by the merging of predesigned sections in a random configuration, creating dungeons with many different placements of enemies and items.

[10] Between dungeons, the player can obtain a limited number of mutations, benefits which grant unique bonuses to the Prisoner's capabilities that last until they die.

After fighting through the island's Malaise-infected locales, the Prisoner reaches the King's throne room and succeeds in slaying the comatose monarch.

The Rise of the Giant downloadable content expands the plot of Dead Cells, providing the game with alternative endings.

If the player collects all five Boss Cells and reaches the throne room, they are able to gain access to an additional level called the Astrolab.

Inside, the Prisoner accidentally knocks over a flaming chandelier, alerting three hostile warriors named Calliope, Euterpe, and Kleio, who are the servants of the island’s Queen.

The studio found that competition in the mobile market required more investment to make profitable games, and decided to switch focus to develop what they considered their "passion project", a game that was "something hardcore, ultra-niche, with pixel art and ridiculous difficulty" that they thought would be a potential risk for gaining player interest.

Motion Twin wanted to have improve the sequel by allowing players to take actions and fight during the night phase, while implementing free to play mechanics.

In 2014, they stripped down the game to a single-player experience between preparation and combat, and took it to an event called the Big Indie Pitch, where the idea came in second place in a contest.

Motion Twin's producer Steve Filby cited The Binding of Isaac as a significant influence, highlighting its item-driven gameplay.

[16] Motion Twin opted to use Steam's early access approach to both gauge player interest and to obtain feedback on game features.

[17] Motion Twin planned for the game to spend about a year in early access before its full release, during which time the content was created and incorporated after player feedback on both bug reports and feature suggestions.

[15] Lead designer Sébastien Bénard estimated that 40 to 50% of the features in the final game were drawn from feedback during early access.

As the game progressed through early access, the developers decided to include a minor story after players found their world compelling.

[21] In January 2018, Motion Twin announced their plans on console development for the Nintendo Switch, PlayStation 4, and Xbox One, with a release predicted in August 2018 to correspond with the Windows' version leaving early access.

[22][23] Motion Twin does not anticipate creating a sequel, and instead focused on adding a robust modding system for the PC versions to allow players to expand the game following release.

[26] Motion Twin released a free downloadable content update to the game called Dead Cells: Rise of the Giant in mid-2019.

[32] A second paid DLC expansion, Dead Cells: Fatal Falls, was released on January 26, 2021, which added new levels, weapons, and a boss.

[34] Motion Twin released a free update on September 16, 2021, titled "Practice Makes Perfect" which added a training room, world map and many other quality of life changes.

These games included Hyper Light Drifter, Guacamelee!, Curse of the Dead Gods, Blasphemous, Skul: The Hero Slayer, and Hollow Knight.

[36][37] Celebrating the 20th anniversary of Motion Twin, the developers revealed the third paid expansion titled Dead Cells: The Queen and the Sea, which released on January 7, 2022.

The update added a new level that can be randomly encountered while playing, which grants the player an opportunity to earn significant sums of gold.

2 update in November 2022 added more homages to other indie games, including Terraria, Hotline Miami, Slay the Spire, Shovel Knight, Risk of Rain, and Katana Zero.

[45] With the game's 35th patch being released on August 19, 2024, Motion Twin and Evil Empire announced that they had stopped further creative work on Dead Cells.

[67][5][68] Reviewers compared the game to the Dark Souls, Diablo, and Castlevania series due to its difficulty and constantly changing levels, while giving specific praise to the visuals and sound design.

[98] In August 2024, roguelike first-person shooter Roboquest released an update featuring characters and items from Dead Cells.