O'Brien was born in Northern Kentucky. He graduated from Conner High School in Hebron, Kentucky in 1983 and currently resides in Tampa. He is of Irish and German heritage. His hobbies involve hunting and target shooting.
O'Brien got his first guitar when he was 11. His mother bought him an acoustic guitar for Christmas. Later, when he started to practice more he received his first electric guitar, a Gibson SG copy. His father also bought him a 1974 Gibson Flying V. His influences include AC/DC, Black Sabbath, Deep Purple, Mercyful Fate and Metallica.
As a guitarist, O'Brien is formally trained, having studied classical guitar. He gave lessons at Buddy Rogers Music, a music store in Florence, Kentucky, where he encouraged his students to listen to jazz, classical, fusion, country and blues and not focus solely on metal. He recalls that his interest in classical guitar probably came from a concert of Andrés Segovia he attended with his father. Segovia remains O'Brien's favourite guitarist and his main inspiration.
O'Brien started playing in a series of bands, sometimes as a touring musician and sometimes as a full-time member. Throughout the 1980s he played in heavy metal bands such as Chastain and Prizoner. In the 1990s O'Brien evolved from heavy metal to death metal. Between 1990 and 1992 he played in the Cincinnati-based death/thrash metal band Ceremony alongside Steve Tucker, Greg Reed and Shannon Purdon. They released a demo in 1992 entitled Ceremony, and an EP called The Days before the Death that did not come out before 2000 and for which O'Brien did the mastering with Mark Prator. After the band's breakup, O'Brien decided to move out of Cincinnati. He relocated to Los Angeles and searched for a new band. Through tape trading he eventually got hired by Nevermore, who at the time were looking for a second guitarist.
O'Brien stayed in the band for two years during which they recorded the EP In Memory and the full-length The Politics of Ecstasy which both came out in 1996. He also toured with the band and took part in a video shoot for the song "What Tomorrow Knows" from Nevermore's eponymous debut album. However, he felt unsatisfied with the band, preferring to be involved in death metal. Following his departure from Nevermore, O'Brien went through a transitional period where he briefly joined Monstrosity as a touring member but remained somewhat inactive for the rest of the time.
In 1997 he was approached by Cannibal Corpse through several relations. After auditioning for the band, O'Brien ultimately became a permanent member replacing Rob Barrett. He has been featured on every Cannibal Corpse album since Gallery of Suicide.
Since his involvement in Cannibal Corpse, O'Brien has been credited on some of the band's more technically complicated songs. One song which has been cited by other band members, both past and current, as the most difficult Cannibal Corpse song is "Frantic Disembowelment" from the album The Wretched Spawn. To this day the band has performed this song live only once. O'Brien has often been complimented by his co-members and other musicians in the death metal scene for his proficiency. In the documentary DVD Centuries of Torment: The First 20 Years bassist Alex Webster stated that "Some of his rhythm parts are as difficult as a solo might be in another band." Drummer Paul Mazurkiewicz commended his contribution to the band's music, stating "He really is a vital part of the Cannibal [Corpse] sound. His songs are awesome and we definitely need his songs on our CDs."
O'Brien himself admitted that he tends to write more technical songs but often regards it as a by-product of the songwriting process rather than an aim in itself. However unlike Webster and Mazurkiewicz, O'Brien does not take part in the composition of lyrics and instead focuses on the music.
In April 2011 O'Brien filled in for Exodus' Gary Holt when Holt left the Slayer European tour to play with his own band. Holt himself had been filling in for the now deceased Slayer guitarist Jeff Hanneman since February 26, 2011, subsequently joining the band.
O'Brien made several guest appearances as lead guitarist. He collaborated on Leather's solo debut album Shock Waves which came out in 1989. He played lead on the track "Balancing Act" which came out as a bonus track for the 1997 re-issue of Lethal's "Your Favorite God" EP. In 2006 he played lead guitar on "Render My Prey" on Spawn of Possession's album Noctambulant. In 2008 O'Brien played guitar on the song "Race Against Disaster" on Jeff Loomis's debut solo album Zero Order Phase. In the same year he made a guest solo appearance on Kataklysm's album Prevail.