In 2006, Ocean moved to Los Angeles to pursue his music career, working at various fast-food and service jobs to support himself. In less than three years, he established himself as a songwriter under the name Lonny Breaux, getting the first name 'Lonny' after his grandfather named Lionel, whom Ocean hung out with often in his childhood. He adopted the stage name Frank Ocean. On February 16, 2011, Ocean self-released the resultingm Nostalgia, Ultra online for free. The mixtape focuses on interpersonal relationships, personal reflection and social commentary. On May 19, 2011, Ocean's record label Def Jam announced its plans to re-release Nostalgia, Ultra as an EP. The single "Novacane" was released to iTunes in May 2011, and the EP originally was set to be released the next month, but was delayed.

In 2012, Ocean released his debut studio album Channel Orange to universal acclaim from critics, who later named it the best album of the year in the HMV's Poll of Polls. It also earned Ocean six Grammy Award nominations and was credited by some writers for moving the R&B genre in a different, more challenging direction. The songs about unrequited love in particular received the most attention, partly because of Ocean's announcement prior to the album's release, when he revealed that his first love was a man. At the 2013 Brit Awards, Ocean won the Brit Award for International Male Solo Artist. On May 28, 2013, Ocean announced the You're Not Dead ... 2013 Tour; a fourteen-date European and Canadian tour that began on June 16, 2013, in Munich.

In February 2013, Ocean confirmed that he had started work on his second studio album, which he confirmed would be another concept album. In July 2016, he hinted at a possible second album with an image on his website pointing to a July release date.The image shows a library card labeled Boys Don't Cry with numerous stamps, implying various due dates. At midnight Pacific time on August 20, 2016, a music video for a song titled "Nikes" was uploaded to Ocean's Connect page on Apple Music and later to his own website. Also on August 20, Ocean announced pop-up shops in Los Angeles, New York City, Chicago, and London for his magazine Boys Don't Cry, and released his second studio album Blonde to widespread acclaim. On July 9, 2018, Blonde was certified platinum by the Recording Industry Association of America (RIAA).

On March 10, 2017, Ocean released a new single "Chanel" on the second episode of Blonded Radio, as well as playing an alternate version featuring American rapper ASAP Rocky. On February 14, 2018, Ocean released "Moon River", a cover of the song performed by Audrey Hepburn in the 1961 film, Breakfast at Tiffany's. On October 19, 2019, Ocean released a new song titled "DHL"on his Beats 1 radio show Blonded Radio and announced 7-inch vinyl singles of two new songs on his website titled "Dear April" and "Cayendo", originally available only as physical singles featuring B-side remixes from Justice and Sango, respectively. On November 1, 2019, Ocean followed up "DHL" with a new song titled "In My Room", which was premiered on Blonded Radio. On August 8, 2021, Frank Ocean officially revealed his first fashion project, "Homer", initially announced by the singer in a Financial Times interview.