Spiner was born in Houston, Texas, the son of Sylvia and Jack Spiner, who owned a furniture store. After Jack's death, he was adopted by Sylvia's second husband, Sol Mintz, whose surname he used between 1955 and 1975. Spiner attended Bellaire High School in Bellaire, Texas, where he was influenced by drama teacher Cecil Pickettthe same drama teacher who coached such people as Cindy Pickett, Randy Quaid, Dennis Quaid, Trey Wilson, Robert Wuhl, and Thomas Schlamme. Spiner would become active on the Bellaire Speech team, eventually winning the national championship in dramatic interpretation. After attending the University of Houston and performing in local theatre there, Spiner moved to New York City, where he became a stage actor, performing in several Broadway and off-Broadway plays, including The Three Musketeers and Stephen Sondheim's Sunday in the Park with George. At the same time, he also had a nonspeaking background role in the film Stardust Memories as one of the silent Felliniesque grotesques on Sandy Bates's train car.
In 1984, Spiner moved to Las Vegas, appearing in several pilots and made-for-TV movies. He played a recurring character on Night Court named Bob Wheeler, patriarch of a family of West Virginia hicks. In 1986 he played a small role as a condemned soul in episode 54 (entitled Dead Run) of the short-lived revival of Rod Serling's Twilight Zone series on CBS. Also in 1986, Spiner made two appearances as characters in season 3 of the television show Mama's Family: Mr. Conroy and Billy Bob. Spiner's first and only starring film role was in Rent Control in 1984. In the Cheers episode Never Love a Goalie, Part II, he memorably played the acquitted murder suspect Bill Grand.
In 1987, Spiner started his 15-year run (on television for 7 seasons and in 4 feature films) portraying Lieutenant Commander Data on Star Trek: The Next Generation. As one of the main characters, he appeared in all but one episode of the series 178 episode run. He reprised his role in the spin-off films, Star Trek Generations (1994), Star Trek: First Contact (1996), Star Trek: Insurrection (1998), and Star Trek Nemesis (2002). Although billed as the final Trek movie for the TNG cast, the ambiguous ending of Star Trek Nemesis suggested that there was a possible avenue for the return of Data. However, Spiner felt that he is too old to continue playing the part and that Data was best presented with a youthful appearance. In addition to the shows and films he voiced his character in several Star Trek video games, such as Star Trek Generations, Star Trek: The Next Generation - A Final Unity, Star Trek: Hidden Evil, and Star Trek: Bridge Commander.
Since his role in Star Trek he also has acted in film, including a role in Independence Day as Dr. Brackish Okun (chief scientist at Area 51). In 1991, he recorded an album of 1940s pop standards entitled Ol Yellow Eyes Is Back, the title of which was a play on the yellow contact lenses Spiner sported as Data and Frank Sinatra's nickname, Ol Blue Eyes. He has since had guest appearances on Law & Order: Criminal Intent, Friends, Deadly Games, Mad About You, Gargoyles, Frasier, Joey, and The Outer Limits, as well as movie roles in Phenomenon, Dude, Where's My Car, Out to Sea, South Park: Bigger, Longer & Uncut, Geppetto, I Am Sam, Master of Disguise, and The Aviator. He had a sizable lead role as Dorothy Dandridge's manager/confidant Earl Mills in the HBO production Introducing Dorothy Dandridge, which was partially based on Mills's book Dorothy Dandridge. Also, he played the lawyer in the 1991 made for TV film, The Ponder Heart.
In 1997, Spiner returned to the Broadway stage, playing the leading role of John Adams in the Roundabout Theatre Company revival of the musical 1776. His performance met with generally positive reviews, and the production was nominated for a Tony Award. A cast recording was released of the revival production. Spiner played the voice of Conan O'Brien in the 1999 South Park movie.
In 2004, Spiner returned to the world of Star Trek when he appeared as Dr. Arik Soong, a perhaps equally brilliant but much sleazier ancestor of Data's creator Dr. Noonien Soong, whom he also played, in a three-episode story arc of Star Trek: Enterprise in Borderland, Cold Station 12, and The Augments. He also briefly reprised the role of Data for the series, providing a voice-only cameo in the Enterprise finale, These Are the Voyages.... Spiner also cameoed in Joey, playing himself. He had also guest-starred in Friends as a man who interviews Rachel for Gucci.
In 2005, Spiner began a role in a short-lived science-fiction television series, Threshold, which was cancelled in November of that year after 13 episodes were produced. In 2006, Spiner appeared in a comedy, Material Girls, with Hilary and Haylie Duff.
During the tenth season of the sitcom Frasier, in the episode Lilith Needs a Favor, Spiner makes two brief cameos as a fellow airline passenger of Frasier's ex, Lilith. When she comments that he must not like flying (in reference to his abnormally pale skin tone) he replies that he is always this pale, a reference to the pasty complexion of his Star Trek character Data.
In March 2008, Spiner performed alongside Maude Maggart in a new radio show/musical called Dreamland. This was released as a CD album (as mentioned on the Radio Show BBC Radio 2, w/Steve Wright, 5 March 2008). In February 2008, Spiner joined the growing league of celebrities who feature on popular online sites like MySpace, under the name of The Real Brent Spiner.
Spiner is not as active in the Star Trek convention scene as many of his co-stars are, although he has participated in the last few years in several conventions around the world, such as in Las Vegas, Milton Keynes and Hobby Star's Fan Expo in Toronto Canada and Dragon Con in Atlanta, Georgia. He is close to his Next Generation colleagues and counts Patrick Stewart, Gates McFadden, Marina Sirtis (in whose 1992 wedding he was a groomsman), and LeVar Burton amongst his best friends. He was seen at the 2007 DragonCon, held in Atlanta, Georgia and more recently at the first ever Collectormania Midlands in Coventry, UK on 1/2 March 2008, along with Star Trek co-star Marina Sirtis. Most recently he made an appearance at the FedCon XVII at Bonn, Germany on 18-20 April 2008, accompanying his fellow Star Trek stars LeVar Burton, Marina Sirtis, John DeLancie, as well as Ren Auberjonois and Michelle Forbes.
Spiner attended the Star Trek Convention in Secaucus, New Jersey from 7-9 March 2008. He was promoting his recent CD Dreamland, an audio experience reminiscent of radio plays from the 1940s. Maude Maggart, sister of singer/songwriter Fiona Apple, is featured on the CD as the female lead.
In 2009, he provided the voice of himself for the Family Guy episode Not All Dogs Go to Heaven.