Fiona Horne started playing in bands when she moved to Adelaide, South Australia, in 1984. Her first band was Sister Sludge, which only lasted for six months until Horne moved back to Sydney. She then formed a punk-thrash band, The Mothers, in 1985. The Mothers started as an all-girl punk band, although the lineup changed a number of times. This was the first band with Horne performing both vocals and guitar. In October 1987, The Mothers, comprising Horne (vocals, guitar), Nat (guitar), Jo Collings (bass) and Rick (drums), released their first single, "Drives Me Wild"/"Get Outta My Life", which was followed in 1989 by the EP, 12-Incher.
In 1990, Fiona formed the industrial-dance-rock band Def FX. The band issued three EPs, Water, in June 1991, Surge, in November and Blink in June 1992 on the Phantom label before signing to EMI. In December 1992 the band released their debut album, Light Speed Collision.
At the 1994 Big Day Out Horne made headlines by appearing topless on stage. In September 1994, they released the EP Post Moronic, which reached No. 43 on the Australian charts. The band were dropped from the EMI label. In May 1995 they released their second album, Ritual Eternal, on their own label, Cicada. They then signed with Universal Music Australia's subsidiary label Grudge, which released the band's third album, Majick, in July 1996. Def FX disbanded in May 1997.
In October 1999, Fiona released her debut single, "Let’s Go Out Tonight", on Air Records. In March 2007, Fiona released her first solo album Witch Web. In 2010, she released the spoken word album Magickal Life-Guided Meditations and Spells for Positive Change, on her own label, Mystic Monkey.
In 2022 Fiona formed a new band, Seawitch. The band released its debut album, Well of Spells, on 21 October 2022, on Cheersquad Records and Tapes. The first single, "Witches Forever", which was followed by a second single, "Force".