Lopatin initially released music under a number of aliases and as part of several groups, including Infinity Window and Astronaut, before adopting the pseudonym Oneohtrix Point Never (OPN), a Verbal play on the name of the Boston FM radio station Magic 106.7. Early OPN recordings drew on synthesizer music, '80s new age tropes, and contemporary noise music. Lopatin released a series of cassette and CD-R projects interspersed with a trilogy of full-length albums: Betrayed in the Octagon (2007), Zones Without People (2009), and Russian Mind (2009). Much of this material was eventually collected on the 2009 compilation Rifts, which brought him international acclaim; it was named the second-best album of 2009 by UK magazine The Wire. Also in 2009, Lopatin released the audio-visual project Memory Vague, which included his profile-raising YouTube video "nobody here". His work during this period would be associated with the early 2000s underground hypnagogic pop trend.

In June 2010, Lopatin followed Rifts with his major label debut Returnal, released on Editions Mego. In the same year, he released the influential limited-edition pseudonymous cassette Chuck Person's Eccojams Vol. 1, which would help inspire the 2010s Internet-based genre vaporwave, and he formed the duo Games (later renamed Ford & Lopatin) with childhood friend Joel Ford. Lopatin's next album, Replica, was released in 2011 on his newly formed label Software Recording, to further critical praise. On it, Lopatin developed a sample-based approach that drew on the audio of 1980s and '90s television advertisements. Also that year, Lopatin participated in the collaborative album FRKWYS Vol. 7 with Musicians David Borden, James Ferraro, Samuel Godin and Laurel Halo as part of RVNG's label series; Ford & Lopatin released Channel Pressure, and OPN was chosen to perform at the All Tomorrow's Parties festival. Lopatin and visual Artist Nate Boyce collaborated on the 2011 Reliquary House performance installation; the music from this project would later be released on the split OPN/Rene Hell album Music for Reliquary House / In 1980 I Was a Blue Square (2012). In 2012, Lopatin collaborated with Tim Hecker on the album Instrumental Tourist.

In subsequent years, Lopatin pursued different stylistic approaches on albums such as Replica (2011), R Plus Seven (2013), and Garden of Delete (2015), signing to British electronic label Warp to release the latter two. He has also participated in several side projects, including the duo Ford & Lopatin and his influential alias Chuck Person, as well as a number of film scores, and collaborations with artists such as Anohni, Ishmael Butler, FKA Twigs, and Tim Hecker.

In 2013, Lopatin signed with Warp Records. His label debut, R Plus Seven, was released on September 30, 2013 to positive reception.Lopatin collaborated with several artists on visual accompaniments, live performances, and internet projects for the album, among them his frequent collaborator Nate Boyce; Jon Rafman; Takeshi Murata; Jacob Ciocci, and John Michael Boling. Also in 2013, Lopatin composed his first film score—for Sofia Coppola's film The Bling Ring, a collaboration with Brian Reitzell—and OPN participated in the Warp x Tate event and was commissioned to create a piece inspired by Jeremy Deller's The History of the World. In 2014, Lopatin supported Nine Inch Nails on their tour with Soundgarden, as a replacement for Death Grips. On October 4, 2014, he presented a world premiere live Soundtrack for Koji Morimoto's 1995 anime film Magnetic Rose. The event took place at the Jodrell Bank Centre for Astrophysics, and featured Anohni on a rendition of the OPN song "Returnal" as well as audio-visual works from Nate Boyce which have been hosted by the Barbican Centre in London, the Museum of Modern Art and MoMA PS1. In the same year, OPN released Commissions I for Record Store Day, featuring several commissioned pieces. He also contributed "Need" to the Bleep:10 compilation in celebration of the online retailer's 10th anniversary. This was followed by Commissions II in 2015.

On November 16, 2017, Lopatin and Park Avenue Armory announced MYRIAD, an expansive conceptual live project dubbed a 'concertscape' and 'four-part epochal song cycle' by the press release on the institution's website. The project is due to be premiered in May 2018. On March 22, 2018, Lopatin released an official trailer for MYRIAD, created by Daniel Swan and David Rudnick, and featuring animation by Nate Boyce. On March 4, 2018, Lopatin formally announced the upcoming release of a new LP titled Age Of on Warp. The album was recorded from 2016 to 2018, and the Oneohtrix Point Never website was updated on the same day.

Born and raised in Massachusetts, Lopatin is the son of Russian Jewish "refusenik" emigrants from the Soviet Union, both with musical backgrounds. Some of his first experiments with electronic music were inspired by his father’s collection of dubbed music tapes, including artists such as Mahavishnu Orchestra and Stevie Wonder, and his Roland Juno-60 synthesizer, an instrument that Lopatin has since used extensively both in the studio and on-stage. In high school, Lopatin played synthesizer in groups with friend and Future collaborator Joel Ford, performing jazz fusion-influenced music at school events. Lopatin attended Hampshire College in Massachusetts before moving to Brooklyn, New York to attend grad school at Pratt Institute, studying archival science. During that time, he became involved in Brooklyn's underground noise music scene.