Similar to the earlier games in the SFC franchise Star Trek Starfleet Command III allows gamers to optimize their ship and allocate power to their ship's systems for different types of strategies such as hit-and-run maneuvers, ambushes or direct assaults. However, Star Trek Starfleet Command III simplifies this process by introducing a new interface for system management that reduces the "micromanagement" of starship control, and allows players to focus on combat. Additionally, for the first time in any Star Trek game players can significantly customize their vessel's weapons, engines, shields and other systems. As players progress through the game, they can acquire better phasers and disruptors, stronger shields and outfit their ship with new special weapons. Star Trek Starfleet Command III also pushes the boundary of the genre by incorporating RPG elements into the experience. Over the course of the game, officers under the player's command will gain experience and acquire unique skills which increases the ships overall efficiency and enable the player to employ advanced attacks. Players can also choose to recruit new and more experienced officers to maximize the overall effectiveness of their ship.

The single player portion of Star Trek Starfleet Command III consists of three separate campaigns where gamers have the opportunity to play as the Klingons, Romulans and the Federation. Initially, players will be given command of a ship with limited capabilities, but after the completion of a successful mission, they will accrue prestige points that they can spend on more powerful ships, system upgrades or officers. In the game players will have the opportunity to control over 25 legendary vessels from Star Trek: The Next Generation such as the Sovereign-class starship, the Romulan Warbird, the Borg Cube, and the Klingon Neghvar-class battleship, as well as several original ship designs. The campaign's progress and the state of the universe can be tracked from a large map that will reflect the political allegiance of hundreds of sectors.

Star Trek Starfleet Command III will also feature a multiplayer "skirmish mode" where players can engage in combat as any of the three playable races from the campaign or as the Borg. Skirmish mode offers instant action-style free-for-all and team-based multiplayer games. Star Trek Starfleet Command III also includes an enhanced version of the Dynaverse 3 multiplayer environment. This persistent online component will feature improved AI and a new system that allows players to join the same fleet, travel together across the map and battle alongside one another for galactic dominance.