Darkspore gameplay is similar that of other action-RPG titles, such as Torchlight and Diablo, with a top-down third-person viewpoint, 'click-to-attack' and 'click-to-move' controls, and special abilities activated by using keys 1-5.

Darkspore has high-rendered modern graphics and textures, and visceral gameplay that moves at a slightly calmer pace than most other 'hack and slash' games to aid its strategic edge.

The player will be able to collect up to 100 heroes, made up of 25 heroes each with 4 variants. Each variant is assigned a letter of the Greek alphabet in order of when they're unlocked (Alpha, Beta, Gamma, Delta) which are of the same type and class and wield the same weapons, but have their own unique look, different stats, and in addition to the 3 abilities which are universal across every variant of the same hero, each of the 4 variants have one separate ability of their own, called 'Variant Abilities'.

Each player can choose a squad deck of 3 heroes to take into every mission, with up-to 3 squads. The right selection and combination of heroes is vital, as their abilities should compliment each others' combat effectiveness, and their types and classes should be selected so as to counter resistances according to the enemies being faced. The player may only control one of the deck at a time, though is able to swap freely between the three. Switching is useful for protecting heroes that are low on health or energy until they can be healed or re-energized, also switching knocks-back enemies and cleanses debuffs. Every hero has its own 'squad ability', an ability which can be used by any of the heroes in the player's squad-deck at any time without switching.

The game's three primary pillars of gameplay are Collection, Customization and Combat. Players will have to rise to the challenge to collect new heroes and many special items, customize and improve those heroes in the editor using the collected items, and then take your selection of the best heroes for the job planet-side to engage in strategic combat and reap the spoils of victory.

Darkspore boasts great replayability, and is designed to have much worth in being played over again several times. The game features a procedural AI Director that dynamically controls enemies, and an assessment system that encourages players to chain multiple missions and earn better loot, a 'Risk versus Reward' system that gives players the option to push their luck rather than cash-out in a risky but exciting gamble. However, if the player chooses to push their luck but fails the following mission, all will be lost. Darkspore leaves plenty of room for experimentation.

The game emphasizes on its co-op elements, as the best campaign experience comes from playing as a team with a friend or two.

Darkspore also features an online Player vs. Player feature, (commonly known as PvP), a component that allows players to pit their customized heroes that they have collected in normal gameplay, against other players' heroes, in a multiplayer battle arena. There will be up to 3 rounds of PvP. Like in the campaign, the player will have a deck of 3 heroes each that the player can swap control of using a universal ability to balance their health, energy, and abilities. The game supports 1 vs. 1 and 2 vs. 2 battles, letting up to four players at a time to join a match.

PvP battles are much more challenging and tactical than that of certain other similar games, as defeating an opponent requires players to use all manner of heroes, abilities, and techniques to eliminate all three of the opponent's heroes, which are likely just as powerful. Online PvP features online matchmaking, ranking, and leaderboards.

Darkspore's co-operative multiplayer campaign is the main focus of the game. Up to four players, each with their own squad deck of 3 customizable heroes, can join in on a campaign game, battling enemies together, forming team tactics, and trading loot.

However, there is one extra challenge in Co-op gameplay, Darkspore Operatives, special enemies that trap a member of your team, as well as drain their health.

There are 5 different Darkspore Agents, each of a different genesis. They are:

  • Cyber - Omicron - Locks down players in a cage whilst healing itself with a repair drone.
  • Bio - Vaulting Amphiod - Cannot be interrupted until dead. They can lock-down two players at once for a short time.
  • Plasma - Magmatic Brute - Summons two minions with 1 hp, Volt, who can lock down a hero and Cinder, who can ignite heros. If these minions die the Magmatic Brute will resummon them. The Magmatic Brute can punch pets while its minions are attacking a hero.
  • Necro - Haunt Strider - Emerges from stealth and snares a hero, and upon getting closer will lock them down.
  • Quantum - Gravitic Confiner - Able to lock down heros at a very long range. Will teleport away when low on hp, appearing shortly after again locking down another hero. Stunning the confiner when it is low hp will prevent it from teleporting until either dead or the stun wears off.

The only way to free that member is to kill the Darkspore Agent, put them to a affect where they don't attack or push them back , putting them in the hands of their fellow teammates.

If there is only one player left, Darkspore Agents will be unable to lock them down.