In the second half of the 22nd century, Starfleet helped the young Federation become a galactic superpower. Its starships could travel farther and faster than those of any other fleet. As a result, Starfleet was often the first to explore uninhabited sectors, to survey solar systems, and to identify rich planets, which would become new Federation colonies. However, these missions for expansion and colonization eventually led the Federation into conflict. If the late 22nd century was the golden age of exploration, then the early 23rd century was the era of imperialism.

Many Federation colonies were established in regions of space claimed by other civilizations. These powers often sought to defend their territory, through passive blockades or direct attacks, against Federation colonies that threatened them. Although some of these Federation colonies were illegal, Starfleet felt a duty to defend all Federation citizens and consistently increased border patrols and planetary defenses. Thus, a vicious cycle of military escalation began. As more Starfleet ships were assigned to patrol and defend new Federation colonies, the threatened opponents reacted more violently. Although the Federation never adopted an official policy of forceful expansion, Starfleet arguably became an instrument of imperialism, the "big stick" of diplomacy that was engaged early and often. The greatest examples of this instrument were the mighty Lancaster-class heavy cruisers, the most powerful warships of the era, and the Paris-class light cruisers, their swift and nimble escorts. The flow of people and material to the frontier was carried by the Giant-class transports, the largest passenger liners of the era. These starships were essential to securing the Federation's borders and expanding the frontier of known space.

Federation Core Worlds, 2215

Starfleet's technological supremacy remained unchallenged until the Federation made contact with the Klingon Empire in 2218. Although not scientifically advanced, the Klingons sought aggressive conflict with the Federation. As the Klingons' technology became more sophisticated, they attacked nearby Federation worlds and killed thousands of citizens. Starfleet brought more combat-oriented starships into service, notably the cannon-mounted Siegfried-class dreadnought and the Avenger- and Predator-class destroyers. Even the Constitution-class heavy cruiser, remembered today as an explorer, was frequently involved in combat during this era. The confrontation with the Klingons became a bitter cold war, which, despite a brief détente in the early 2250s, grew ever more violent and led to the Four Days' War in 2267.