He was portrayed by Colm Meaney.
O'Brien was born in Ireland on Earth to Michael and Megan O'Brien. As a child he built ships inside bottles. His father pushed him towards accepting a posting to the Aldebran Music Academy, however O'Brien instead enlisted in Starfleet at the age of 17.
He served on a large variety of postings throughout his career in the Federation Starfleet. He was posted to the USS Rutledge prior to his assignment on board the Enterprise. While posted to the Rutledge he was present for the Setlik III Massacre and the aftermath. O'Brien was forced to take a life for the first time in his life when he fired upon a Cardassian soldier with a phaser that had been set to maximum.
In 2364 O'Brien was posted to the Enterprise-D under the command of Jean-Luc Picard. Initally working as a command division crewman he served as a helmsman during the Enterprise's first encounter with Q. He would later serve a tour in security before being assigned as a transporter chief.
O'Brien would become good friends with many of his fellow crewmates, including Data, Geordi LaForge, William Riker, Wesley Crusher, and Worf, Son of Mogh. He would be very highly thought of by Captain Picard. In 2367 he married Keiko Ishikawa, and would later have a daughter named Molly and son Kirayoshi with her.
In 2369 O'Brien and his family moved to Deep Space Nine after O'Brien was transferred to the station to become the Chief of Operations. As on the Enterprise, O'Brien became close to the command staff, and was especially good friends with Doctor Julian Bashir.
A misunderstanding in 2372 led to the Argrathi subjecting O'Brien to twenty years of simulated imprisonment in the space of a few hours. O'Brien was traumatized by the imprisonment simulation, especially when he killed a fellow inmate over a few scraps of food. He had considerable difficulty readjusting to normal life after being freed, leading to him almost striking his daughter. At his wits end O'Brien set a phaser to level 16 and was preparing to commit suicide when Dr. Bashir intervened and managed to find out about O'Brien killing a friend in the simulation. Bashir provided O'Brien with medication but said he could not remove the false memories, that O'Brien would have to come to terms with them. O'Brien attended intensive counseling sessions to help him move on.
After the end of the Dominion War in 2375 O'Brien decided to move back to Earth with his family, accepting a position as a Professor of Engineering at Starfleet Academy. The following year he helped the crew of DS9 during the Parasite incursion in the Bajoran system, and was present on Bajor when the Bajorans finally joined the United Federation of Planets.
When Keiko accepted a position on Cardassia to oversee the reconstruction of Cardassia's ecology after the Dominion War, O'Brien accepted a transfer to the Starfleet Corps of Engineers and was posted to the team working on Cardassia as part of the Federation relief efforts.
In 2383 O'Brien was placed in charge of building the new Deep Space Nine after the destruction of the original station. After the new station was completed O'Brien became the Chief Engineer. With Keiko's work on Cardassia completed, she and their children joined him on DS9.