The Odyssey arrived at Deep Space 9 shortly after it was announced by the Jem'Hadar that they had taken Commander Benjamin Sisko prisoner in the Gamma Quadrant. With news of this, Starfleet suspended all wormhole traffic, and ordered the Odyssey to proceed into the Gamma Quadrant to investigate the Jem'Hadar's threat.
During the operation, the Odyssey, along with the USS Mekong and USS Orinoco, engaged three Jem'Hadar attack ships. It was quickly discovered that the Odyssey's shields were ineffective against the Jem'Hadar's phased polaron beams, and she took significant damage from multiple direct hits. Realizing this, Captain Keogh ordered power from the shields be diverted to the phasers in order to inflict more damage on the enemy.
The Jem'Hadar took advantage of this opportunity and made a suicide run at the Odyssey as she tried to retreat. The attack ship collided with the Odyssey's secondary hull and the ship exploded seconds later with all hands lost. Fortunately, most non-essential crewmembers and all civilians had been offloaded at DS9 prior to departure, saving hundreds of lives. (DS9: "The Jem'Hadar")
The destruction of the Odyssey, which became the cornerstone for the Dominion cold war, showed the Federation that the Dominion was a potent and dangerous threat. In response to this provocation, the USS Defiant was brought out of the warehouse and put on active duty. (DS9: "The Search, Part I")
USS Odyssey personnel
|USS Challenger • USS Enterprise-D • USS Galaxy • USS Odyssey • USS Venture • USS Yamato • Unnamed|
The Odyssey's dedication plaque bore a quote from Arthur C. Clarke's 2001: A Space Odyssey: "Its origin and purpose, still a total mystery." This plaque was located on the rear wall of the bridge. In August 2020, DS9's writer and producer Ira Steven Behr shared on his Twitter account a picture of the Odyssey's dedication plaque, showing the commissioning on stardate 41263.5 (around 2364). 
The bridge shown in the episode was a completely different set than the one used for the USS Enterprise-D. The hollow model of the USS Enterprise-D which was blown up for TNG: "Cause and Effect" was again used to blow up the USS Odyssey.
According to the Star Trek: Deep Space Nine Companion, the show's writers intentionally made the Odyssey a Galaxy-class ship to emphasize that the Dominion was a much more threatening force than anything the Enterprise-D had encountered during TNG, with the exception of the Borg. The writers wished to show that even the Enterprise-D would stand no chance in the same situation.
In the Lost Era novel The Buried Age, by Christopher L. Bennett, Starfleet briefly considered giving command of the Odyssey to Captain Jean-Luc Picard before naming him the commanding officer of the Enterprise following the early retirement of the Enterprise's original intended captain, Thomas Halloway.
In the The Next Generation Relaunch novel, Greater Than the Sum, also by Bennett, it is revealed that all non-essential personal from the Odyssey were evacuated off-ship prior to entering the wormhole. This included the fifteen-year old T'Ryssa Chen (β), who would later serve on the USS Enterprise-E from 2381.
In the video game Star Trek: Armada, a Galaxy-class ship named USS Odyssey appeared in the mission "Once and Again", transporting Ambassador Spock to a peace conference between the Klingon Empire and the Romulan Star Empire to help defend against a Borg invasion shortly after the Dominion War.