Delta Rising's story leads off directly from the "Solanae Dyson Sphere" episode where the Romulan Republic, Federation, and Klingon Empire collaborated in the discovery and exploration of a Dyson sphere in the Delta Quadrant, and came into conflict with other parties seeking to use the sphere: first the Voth, then the Undine. The episode's final mission "Surface Tension" saw Earth and Qo'noS come under direct attack by the latter, leading to an armistice that officially ended the Federation-Klingon War of 2405-2410.
In Delta Rising the player begins to investigate the Delta Quadrant for the first time since Star Trek: Voyager over thirty years earlier, with the three powers, now calling themselves the Alpha Quadrant Alliance, dispatching a multinational military expedition from the Jenolan Dyson sphere into the Nekrit Expanse region. They soon come into conflict with a renewed Vaadwaur Supremacy and must forge an alliance of local races to defeat them.
Delta Rising added another tier to the Reputation system and raised the level cap from 50 to 60 for the first time since the game was released. It also added Tier 6 starships and featured the debut of additional bridge officer specializations, beginning with Intelligence officers.
At release Delta Rising featured guest appearances by five members of Star Trek: Voyager's main cast, who reprised their old roles for the expansion.
- Tim Russ plays Tuvok, now a rear admiral and commanding officer of Voyager, in a recurring role in the storyline. Russ had previously voiced the character in the Legacy of Romulus missions "Fluid Dynamics", "A Step Between Stars", and "Surface Tension".
- Ethan Phillips reprises the role of Neelix beginning in "Reunion".
- In the Kobali arc, Garrett Wang returns as Harry Kim, now a captain and CO of the USS Rhode Island.
- Jeri Ryan returns as Seven of Nine in "Revelations" and "Alliances", and later appears in the "Borg Disconnected" team PVE mission assisting the Borg Cooperative.
- Robert Picardo returns as the Doctor beginning in "All that Glitters".
In addition, Denise Crosby returned as the former Empress Sela in the featured episode "What's Left Behind", released one month after launch, while Kim Rhodes returned as Jhet'leya in the 5th anniversary mission "Dust to Dust" (a direct sequel to her previous appearance in VOY episode: "Ashes to Ashes").
The Season 10 update, launched 21 April 2015, introduced a new episode entitled "The Iconian War", with Robert Duncan McNeill returning as Captain Tom Paris, and Lisa LoCicero voicing his daughter Lieutenant Commander Miral Paris (who had previously appeared in the "Klingon War" episode with voice work by a different actress). Additionally there was an appearance by Aron Eisenberg voicing Captain Nog.