Maaya Sakamoto launched her music career in 1996 at the age of fifteen with the single Yakusoku wa Iranai, which served as the opening theme for the anime series The Vision of Escaflowne. The song was composed by Yoko Kanno, beginning a partnership that would define the first phase of Sakamoto's musical identity. Her debut album Grapefruit followed in 1997, and she released her second album Dive in 1998. Both albums, along with her early singles and compilation tracks, were produced almost entirely by Kanno, with lyrics primarily written by Yuho Iwasato and occasional contributions from Sakamoto herself. She wrote the lyrics for the songs Pilot and Call Your Name, both included on her first compilation album Single Collection+ Hotchpotch, released in December 1999.

Throughout this early period, Sakamoto established herself as a prominent interpreter of anime theme songs. In 1997, she released the single Gift, which served as an ending theme for CLAMP School Detectives. The following year, she performed Kiseki no Umi, the opening theme for Record of Lodoss War: Chronicles of the Heroic Knight. Her 1999 single Platinum became the third opening theme for Cardcaptor Sakura. Her second compilation album Single Collection+ Nikopachi, released in July 2003, included the single Hemisphere from RahXephon, Gravity from Wolf's Rain, and Tune the Rainbow from the RahXephon movie.

The album Shonen Alice, released in December 2003, marked the end of Yoko Kanno's essential role in producing Sakamoto's music. Starting with her fifth studio album Yunagi Loop in October 2005, Sakamoto began collaborating with a wider range of songwriters including H-Wonder, Takeshi Nakatsuka, Takayuki Hamasaki, and Shoko Suzuki. She also continued writing her own lyrics more frequently. The extended play 30 Minutes Night Flight followed in March 2007.

In 2008, Sakamoto reunited with Yoko Kanno for the single Triangler, the opening theme for Macross Frontier. The song reached number three on the Oricon singles chart and received a platinum certification. Her album Kazeyomi, released in January 2009 under the FlyingDog label, featured this hit single alongside collaborations with musicians such as Koichi Tabo, Kaori Kano, Aco, and Katsutoshi Kitagawa, who would become a longtime member of her live band. That same year, Sakamoto held her first live tour, Maaya Sakamoto Live Tour 2009 Kazeyomi, and released her fifteenth-anniversary greatest hits album Everywhere, whose title track became her first self-written and self-composed song.

Sakamoto achieved her first number one record on the Japanese charts with her sixth studio album You Can't Catch Me, released in January 2011. The album featured contributions from Atsushi Suemitsu, Suneohair, and Hideyoshi Sakurai. Later that year, she released the extended play Driving in the Silence, which reached number three on the charts. Her seventh studio album, Singer-Songwriter, released in March 2013, represented a significant artistic milestone as an entirely self-produced work for which she wrote both the music and lyrics for every track.

Additional anime theme songs from this period include Ame ga Furu, the ending theme for Linebarrels of Iron released in 2008, and Buddy, the opening theme for Last Exile from 2011. Sakamoto continued releasing studio albums including Follow Me Up in September 2015, Kyo Dake no Ongaku in November 2019, and Kioku no Toshokan in May 2023. She also released the compilation album Single Collection+ Mitsubachi in November 2014 and Single Collection+ Achikochi in July 2020.

Throughout her career, Sakamoto has been known for a musical style that spans pop, folk, jazz, and orchestral balladry. Her voice is characterized by clarity and a breathy timbre well suited to both energetic pop-rock arrangements and atmospheric, mystical pieces. Her ability to sing in English, which improved markedly over her career, is demonstrated on songs such as Gravity, recorded almost entirely in English. Frequent collaborators across her discography include lyricist Yuho Iwasato, English lyricist Tim Jensen, composer Shoko Suzuki, and producer and composer Yoko Kanno, whose early mentorship and intermittent later collaborations shaped Sakamoto's artistic trajectory.