The Syndicate was originally a wholly Orion organization, complete with laws, uniforms and legitimate trade with other worlds. In the 22nd century, the Syndicate was already operating and focused on slave trade. The Orion government officially took a neutral stance in the 23rd century. By the late 23rd century other races, such as Humans were mostly in control of the syndicate.

During the 22nd century, the Orion Syndicate controlled an area of space bordering the Klingon Empire. The area of space between the two powers was a volatile and lawless region known as the Borderland. It was in this region that a group of Augments, relics from Earth's Eugenics Wars, attacked a Klingon Bird-of-Prey in 2154, murdering the crew and stealing the ship. In order to avert a war with the Empire, Enterprise NX-01 was sent into the Borderland in an attempt to locate the Augments. While on this mission, however, Enterprise was attacked by an Orion Interceptor, and nine crewmembers were kidnapped. The crewmembers were taken to a processing station on Verex III, where they were intended to be auctioned off as slaves. Although Captain Archer was able to rescue his crewmembers, his actions in stealing Orion "property" made him a wanted man in the Syndicate. Later that year, an Orion named Harrad-Sar attempted to kidnap Archer and deliver him to the Syndicate. It was during this incident that it was learned by the Enterprise crew that Orion females, previously thought to be little more than commodities to be bought and sold, were actually in charge of the Syndicate, controlling the males via highly potent pheromones.

In 2155, at the founding of the Coalition of Planets, the Tellarites and Coridan III reached an accord on trade sanctions against the Syndicate. However, Earth's government did not wish to provoke the Syndicate into embargoing trade with any Coalition worlds, such as Coridan or Tellar, for fear that they would withdraw.

During the early 23rd century, the Orion Syndicate was described as an active trading network, functioning as a plutocratic republic, lead by Orion merchant lords. Its trade stretched beyond Orion space and beyond the limits of space explored by the Federation but soon various other underworld organisations including the Sicilian Cosa Nostra and Russian Mafia, the Japanese Yakuza and the Chinese Tongs and Triads from Earth; renegade Am Tal agents; houseless Klingons; Naussicaans and other lowlifes began encroaching and infiltrating the Syndicate. In the 2220s a notorious young Yakuza killer and saboteur named Suru Yoshitoni became famous for his brutal role in the reformation and reorganinisation of the Syndicate.

The Syndicate took advantage of factional conflict on Coridan to fund, construct and manage a number of illegal dilithium mining operations and one-sided trade agreements. Following a push for Coridan to join the Federation in the 2260s, the Syndicate attempted to sabotage the Babel Conference of 2267, by inserting Thelev as an Andorian aide to assassinate the Tellarite ambassador Gav and frame the Vulcan ambassador Sarek. The plot was unsuccessful.

The Orion government is very difficult to define, as the only bodies of any real power are the Cartels. These cartels do not attempt to do much in the way of governing the Orion people, though they position enough of a council in place to maintain stability on the planet. Their only strict enforcement is pheromone testing when an Orion child comes of age, to screen for the best viable recruits. Their key aim is to maintain their race in a stable and preferential position within the politics of the Alpha and Beta quadrants. Other bodies do exist, such as the Orion Free Traders and the Orion Union, but speculations as to whether these other bodies are in fact just other divisions of the various cartels are ongoing. The Orion Syndicate is the largest and most powerful of eight Orion pirate cartels, the others being the Orion Cartel, Crimson Shadow, Camboro, Prime Industries, Tiger Heart, Beast Raiders, and the Wyldefire Compact. It is reputedly headquartered on Botchok (Rigel VIII), a likely Orion homeworld, but wisely keeps its overt actions far away, operating primarily in the Alpha Quadrant. It also maintains headquarters on Farius Prime.

The military of the Syndicate is notably inferior compared to other species, with no grand fleets ready to do battle. Instead, the Orions' great power is that of knowledge, misdirection and subterfuge. A carefully spun web of diplomats, spies, courtesans and dozens of other roles continually feeds back information to the main body of the Syndicate from all across the Alpha and Beta Quadrants. When action is necessary, the Orion web turns into a noose that spans across dozens of systems, converging on a single point of action.

The Syndicate rarely fights their own battles, and instead takes great pleasure in orchestrating others to do battle for them. Even when direct action is required, it is rarely in the form of a space battle; often ships pursuing an unknown threat will find themselves called to withdraw, an official assassinated, a dilithium plant sabotaged, a colony struck with a bioweapon, all without realising how close they are to a Syndicate stronghold.

A great enjoyment for the Syndicate is intricately woven strategies that span across starsystems and could destabilize an entire sector when executed properly. A suicide pact amongst Syndicate members in dire straits also eliminates any cause to place blame on the Orions, whilst a few tokens pre-placed in key locations are enough to draw blame to another unknowing party. Even those few agents who defect from or abandon the Syndicate are often allowed to do so on a tactical basis; those whom possess information that could compromise key endeavours however, are promptly eliminated.

The Syndicate operates, either covertly or openly, dozens of gambling halls and slave markets. While most of their crimes are heinous, it was the last that was of the greatest concern to the Federation. The Federation issued dozens of sanctions against the Syndicate in the last several decades, though the enforcement of those sanctions had been inconsistent from administration to administration. There had been attempts by Starfleet Intelligence to infiltrate the Syndicate, but every attempt had ended in failure, with the Starfleet operative exposed and eliminated. The Syndicate was very careful who it lets into their confidences, and their membership process was both expensive and time-consuming and not without risk. As yet, Starfleet had been unable to plant a reliable agent into the Syndicate.

In all, the Syndicate is a ruthless organisation, whose activities are both covert and open, ranging from simple gambling and piracy to overarching plots that resulted in entire systems going dark. With no clear agenda for an onlooker to realise, and all infiltration attempts from Starfleet ending in failure, the Syndicate is perhaps as big a threat to the great powers of the Alpha and Beta Quadrants as they are to each other, who unknowingly expend great resources as they flail aimlessly within the hidden agenda of the Syndicate.