Willcox was born in Kings Heath, Birmingham. Her father Beric Willcox ran a successful joinery Business and owned three factories. Her mother Barbara Joy, née Rollinson, was a professional Dancer with whom he fell in love after seeing her on stage in Weston-super-Mare with Flanagan and Allen, and married in 1949. Barbara had to give up her career after giving birth to Nicola (b. 1950) and Kim (b. 1953), Willcox's older sister and brother, respectively. Asked why her parents might have called her so, Willcox said in a 1981 interview: "I don't know, they won't tell me, but it's definitely my birth name. There is a town in Texas, called Toyah, and Toyah in Red Indian means 'water'. My parents deny that's where they got it from".

Since Willcox's move to London in the mid-1970s her acting and musical careers developed in parallel, causing lots of misunderstanding. "I think people found me either fake, or couldn't put me in a compartment", Willcox later commented on the way her work in theatre and the reputation of "high priestess of punk" collided. In 1980 Writer Paul Morley described Willcox's roles as having had "great attraction" and being "bright boosts". Solidly established ("and undeniably hot", in Morley's words), she had at the time much less credit as a musician, desperately wanting, meanwhile, her music to be as accepted as her acting. On the way those two worlds interacted, Willcox's commented: "It's difficult to compare the two worlds and say why you're doing both. I generally just do whatever I want to do next. I'm still the one person about, I think, who's managed to keep the two careers completely separate. Very little of my music gets involved with my acting, and I wouldn't like it to. I like doing both music and acting. I get a lot of inspiration from acting and the music. Doing a play like this leaves the days free to work on music. It's just perfect. I need to work day and night time, so having both enables me to do that."

After her O-levels (which she took late, having lost a year to have corrective surgery on her feet) Willcox left school at about 17 and went straight to Old Rep Drama School in Birmingham. "Already by then I was known in Birmingham for being the oddball that walked around with dyed hair. And you've got to remember that this is pre-punk, this was about 1973–74", she later recalled. While in drama school she had to pay her fees because she was the one of her year who didn't get a grant (the man who took her grant meeting wrote down on a piece of paper, which she saw: "She has a lisp and isn't attractive"). "I worked in all the theatres in Birmingham so I'd go to drama school from 10 to 5, then I'd go to the Alex Theatre or the Hippodrome Theatre and I'd dress the stars who were on tour", she recalled. All of those stars without exception, including Judy Geeson, Simon Williams and Sylvia Sims, took a liking to her; by this time she was known in the theatre clique as the "Bird of Paradise".

Willcox attended a private girls' school where she was noted for absence from the class room and for setting off alarm clocks during a speech by a visiting MP, Future Prime Minister Margaret Thatcher. Suffering from dyslexia, which, by her own admission, turned her into an "angry, rebellious" teenager, she achieved just one O-level pass in music. The ambition to sing and act started at about nine. "I was an incredible dreamer when I was at school. I just felt trapped. I wanted to escape, really", she remembered. This had to do also with her upbringing which she described as "very strict". As a teenager, obsessed with aliens and the concept of alienation, Willcox felt she could not fit in with anything. "I loathed suburbia, I loathed the idea of getting married and having kids. I just thought: 'Where the hell do I belong?'" she recalled. In 1974 Willcox started to exercise her rebel instincts in experimenting with hair. "I just looked like something off another planet. And I was very very lonely. No one would come near me. Buses wouldn't pick me up, boys wouldn't come near me", she remembered.

Willcox's performance in Glitter (1976), which some years later she remembered as embarrassing, provided nevertheless a crucial impulse to start musical career of her own. "Inspired by the band, the equipment, the volume, the ambience... my mind was set. I had to put a band together myself, or get into one... quick!", she said. In 1977, while with the London's National Theatre playing Emma in Tales from the Vienna Woods, Willcox fronted a band called Toyah which featured Joel Bogen on guitar, Mark Henry on bass, Steve Bray on drums, Peter Bush on keyboards, and herself on vocals, cutting "a very striking visual image at this time with bright orange hair with pink tips". She never considered herself a musician. "I was writing poetry. Most of that poetry went onto an album called Anthem. But I've never really been a musician. I'm a lyricist primarily. So back then I was writing poetry and learning what I loved about a song", she later recalled.

In the summer of 1977, a National Theatre actor, Ian Charleson (best known for his later role in Chariots of Fire), thought that Willcox was someone that his friend, film Director Derek Jarman, should meet and took her to tea on Tregunter Road in Fulham at Derek's flat. The Director picked the script of what later proved to be a seminal punk epic Jubilee (called Down with the Queen at the time), said: "it's a punk movie and I don't know what we're going to call it. But it's fun, it's anarchic", and threw it on Willcox's lap, saying: "Pick any part you want". "So I picked Mad because she had the most lines in the film. And Derek then said: 'Of all the characters, if any have to be cut because of lack of money, it's going to be Mad. Because she is superficial, she doesn't serve a purpose', and I said: 'How wonderfully anarchic, I still want it'", Willcox remembered. In a month's time he did have to cut Mad from the film, but, seeing Willcox greatly upset, gave up his fee on the film so that she could play the role she was craving for. "After that Derek became like a surrogate father because he knew what it was like to go hungry and so did I", Willcox recalled. Later she cited Jarman as one of her greatest inspirations: "Derek Jarman I just love to death because he had no compromise. We went hungry when we made Jubilee. Derek literally had nothing to eat halfway through the film, he completely ran out of money. There was nothing in the coffers and he just refused to sell out and have any form of advertising or any form of sponsorship. Everything offered to him might have diluted the message of the film he turned down. So his spirit I feel very fond of. He was a great man."

In London, Willcox lived in a place called "Mayhem", the converted British Rail warehouse serving as a studio that started off as a "sort of over ambitious multi-media idea and the whole idea was for anyone to go in there and try and create something", according to Willcox. It was there that the band Toyah recorded their first demos. For the lack of proper bed she slept for a while in a "second-hand" coffin, reportedly used by the French Red Cross to transport victims of fatal accidents. While doing the film Quadrophenia (1979) Willcox was getting a lot of press and the band was doing well. Up to two thousand people would turn out at gigs, which were huge crowds for an unsigned band. They did a showcase for Safari Records and the label promptly signed them. "Which amazed me, because I'm a live performer, I need my audience, I need my interaction and we were performing in a small rehearsal studio that smelt of beer and piss. But this worked well. It meant I could go back to Quadrophenia and say to Sting: 'I've just been signed!'" Willcox remembered. The band had its first success with the debut single "Victims of the Riddle", which topped the UK Indie Charts. Then came the Sheep Farming in Barnet EP, produced by Steve James and Keith Hale. Initially released in Germany, in 1979 it was re-released as an LP, comprising the original six tracks, "Victims of the Riddle" A and B sides and three tracks that were previously unavailable on vinyl. Willcox's second album, The Blue Meaning, went up to no. 40 in the UK Albums Chart in June 1980. By this time she severed all ties with punk aesthetics. "I don't use punk whatsoever because my philosophies are so different, my morals are so straight. I'm not a punk, I'm a modern woman", Willcox said in a 1980 TV interview.

Willcox often emphasised that music and acting for her complemented one another: "I got to do both. I like both for totally different reasons but I find if I escape for a few months from music to do some acting, then when I'm acting I'll probably write a lot of lyrics. I like being busy the whole time. I like having to think the whole time. When I'm at my tiredest I get my best ideas. So if I had to do one career I would find it incredibly frustrating coz it wouldn't satisfy my imagination enough", she said in an ATV 1980 documentary. "There was a time when I was doing two movies and an album. Quadrophenia and Quatermass and the Sheep Farming in Barnet LP. I didn't sleep for two weeks and I was very happy", Willcox told Paul Morley in 1980. On distinction between the two careers, she remarked: "When I'm acting I'm someone else's puppet. I'm the director's or writer's puppet. You feel that you are eating other people's minds to create a totally separate person. You're creating something that doesn't exist, and it's great. You feel like a creator", adding: "I've got two personalities that both need feeding at the same time. I couldn't tell you what they are. I've got the snob in me and I've got the commoner in me. The snob does the acting and the commoner the music".

In January 1981, the live album Toyah! Toyah! Toyah!, recorded at the Lafayette Club in Wolverhampton the previous June, made it to the Top 30, backed up by a TV documentary Toyah. By now the original band had broken up. "I played mother to that band for two years and they just walked out on me. It's left me bitter, but I know I can survive without them", Willcox said in an interview. The new line-up consisted of Phil Spalding, Nigel Glocker and Adrian Lee, only Joel Bogen remaining and Toyah. 1981 saw Willcox's strengthened presence in the charts with hits such as Four from Toyah EP (no. 4, February 1981, including "It's a Mystery"), the third album Anthem that went to no. 2 in May 1981 to be later certified platinum, "I Want to Be Free" (no. 8, June 1981), "Thunder in the Mountains" (no. 4, October 1981) and Four More from Toyah EP (no. 14, November 1981). She became one of the first acts to score regularly in the UK Singles Chart with EPs, which were also successful on an international level. At the end of the year Willcox won the Smash Hits' reader's poll in two categories: Best Female Singer and Most Fanciable Female (beating Kim Wilde to the second place). In 1981 she alone, according to Safari, sold in the UK more units than the whole of the Warner Bros. put together.

In 1982 The Changeling album was released, produced by Steve Lillywhite, marking a turn for a more goth-tinged sound, it went up to no. 6 in the UK. "Changeling was a reaction because I wasn't ready to write. I should have had another six or twelve months to address the album. It was all written in the studio. I think it's a good album, it says something very powerful. But it was a painful album and a very painful period in my life where I just had to move back into acting, which was Trafford Tanzi", Willcox remembered. The Changeling was followed in the same year by a double live album Warrior Rock: Toyah on Tour. Also in 1982, Willcox appeared in Urgh! A Music War, a British film released in 1982 featuring performances by punk rock, new wave, and post-punk acts, filmed in 1980, in which she performed her hit, "Danced". Three more of her singles, "Brave New World", "Ieya" and "Be Proud Be Loud (Be Heard)" have made it into the Top 50.

The making of Love Is the Law (1983) was the happiest period of her life, according to Willcox, when "everything was going right. I was starring in a stage play called Trafford Tanzi, which won me especially huge critical acclaim, and I was about to star in a film, The Ebony Tower with Lord Laurence Olivier just as soon as the album was finished. It was a killer timetable but I loved it with a passion", she remembered. By this time, though, her popularity started to decline: the album reached no. 28 (with singles "Rebel Run" and "The Vow" peaking at no. 24 and no. 50 respectively), but the 1984 greatest hits compilation, released by K-tel and called confusingly Toyah! Toyah! Toyah!, failed to chart.

Toyah Willcox disbanded her group, signed to a major label, Portrait Records, and in 1985 released the solo album Minx which contained several cover versions including Alice Cooper's "School's Out" as well as her own hit "Don't Fall in Love". In 1986 Willcox married UK Guitarist Robert Fripp and formed with him a new band Sunday All Over The World which released critically acclaimed Kneeling at the Shrine album. The same year she also sang lead on the Tony Banks' track "Lion of Symmetry". Her next solo album Desire (1987) was less successful although the single with her version of "Echo Beach" made it Top 50. Then in 1988 Prostitute came out, an album through which Willcox vented her frustrations which started to accumulate as a result of having made the transformation "from all-powerful Artist to invisible woman" in the course of just one year of marriage. This experimental concept album, marking a considerable divergence from previous works, was released on E.G. Records. The attitude to Prostitute, according to Willcox, in the UK and the US was radically different: "In the UK, when my management tried to sell it to the music reps, an awful lot got up and walked out of meetings; all male I hasten to add. In America, Billboard magazine said it was the dawning of a new era for me as a Producer and that it was an antidote to Madonna. I started to receive mail from professors at eminent universities telling me they played the album at their lectures as an Example of the new way of thinking coming from contemporary women." Robert Fripp joined his wife on her 1991 album Ophelia's Shadow (1991) which, along with Dreamchild (1994), received good reviews. In 1996 Willcox released The Acoustic Album on Aardvark Records, featuring strings from Royal Philharmonic Orchestra and produced by Oliver Davis.

Willcox married Robert Fripp of King Crimson in 1986 in Poole, Dorset. "I got married because I had found my soul mate, not because I wanted to be married", she said in a 2008 interview.

In 1987 Willcox was invited to make a speech at Women of the Year ceremony in presence of H.R.H. the Princess of Wales, expressing her views on the subject of how being disabled incites creativity and craving for fuller life experience.

At the launch of her autobiography in 2000, the singer said: "We had a very violent relationship together. I was the violent person. And I didn't want her to kind of suffer by the book and I hope I represented her very well. Coz she really was a wonderful woman with a child from 'hell'." In another interview of the time, Willcox said: "My mother taught me how to walk, she was one that was trained to give me the physiotherapy to straighten my own spine so twice a day we would go through this routine. So she was disciplinarian in my life from a very – well right from when I can remember. So it was natural she was the first person I should rebel against. And I regret that our relationship was very often violent. And [now] I feel very strongly towards my mum that she sacrificed everything to give me the freedom I have today."

In 2001 Willcox was awarded an honorary doctorate by the University of Central England in recognition of her achievements in performing arts, media and broadcasting. The 2001 May issue of Q magazine named Willcox number 48 in their top 100 Greatest Women in Music poll, as voted for by readers of the magazine. She returned to music in 2002 with new material for a limited edition Little Tears of Love EP and a one-off preview concert at Ronnie Scotts. The same year she sold out eleven stadium gigs for the Here and Now tour. She continued to perform with her band, releasing a mini-album Velvet Lined Shell in 2003 on her own record label, Vertical Species Records, showcasing a darker, edgier direction. In 2004 she performed as part of The Best of the 80s tour in the UK alongside Nick Heyward, Curiosity Killed the Cat and Altered Images. A live DVD followed in 2005, the year that also saw two parts of The Safari Records Singles Collection being issued.

In 2002 Willcox became a prominent opponent of planned accommodation centres for asylum seekers near the Worcestershire village, Throckmorton. Protesting together with more than one thousand villagers, Willcox said: "The villagers are not anti-asylum seekers and they are not racists", adding that "it was not a simple black and white issue". Commenting on the Government's plans to build asylum centres in other rural areas, Willcox said: "This is only the first of 15. The sheer scale is mind-boggling. This is a small country – it's all happening illegally."

From early childhood, Willcox was aware she did not fit into gender stereotypes. In an all-girls school she was always a tomboy, very aggressive and physical, frequently in fights. In 2003 Willcox remembered: "The rebellion came easy since most of my life up until I was a teenager I had to play a gender role. I didn't like to be a female and I didn't like to be a boy either, I just wanted to be a person and I was acutely aware of this very early on in life, about the age of four. I loathed dolls, I loathed dresses, everything that had to do with femininity I couldn't bear. And it was forced on me with such passion that I thought: 'If I don't fight it I'm gonna be stuck with it for the rest of my life'".

For the first 19 years of their marriage the couple lived largely separate lives due to the demands of their careers: she in Pershore, Worcestershire, UK, Fripp in the US, and rarely saw each other for more than 12 weeks every year. "But [Robert is] in semi-retirement now, so he's home, I cook for him twice a day and I really like it. We're having lovely lovely autumn years of our marriage, it's really nice", Willcox said in a 2006 radio interview.

In November 2007 Willcox took on the role of sponsoring the Black Country Urban Park for the People's £50 million Big Lottery Fund. In April 2008 Willcox took part in the Great Walk to Beijing alongside other celebrities to raise money for Olivia Newton-John's cancer charity.

In the 2000s Willcox had a busy schedule with theatre commitments, including appearing on stage in London's West End performing the title role of Calamity Jane (nominated for an Evening Standard Award for Best Musical) at the Shaftesbury Theatre in 2003. In June 2008 Willcox appeared on Living with the Dead on Living to share her experiences living in her haunted home. On 24 July 2008 Willcox appeared on UK ITV1's This Morning to discuss her role as a vampire in rock musical Vampires Rock. Toyah has also appeared in shows looking back on popular culture, including the I'm a Celebrity series, and various 'Top 100 favourite' shows. More recently, Willcox played Queen Ivannah in Snow White and the Seven Dwarfs at the Lyceum in Sheffield for the 2009 Christmas season. In October 2009 she made a guest appearance in the BBC drama series Casualty. Willcox has also been heard on radio including the 2002 BBC Radio 4 series The Further Adventures of Sherlock Holmes. She is also played the widow Fantine in Focus on the Family radio theatre's version of Les Misérables. In December 2006 she joined the radio drama series Silver Street on the BBC Asian Network as Siobhan Brady. In November 2017 she played Queen Elizabeth in a theatre adaptation of Derek Jarman's film Jubilee at Manchester Royal Exchange Theatre.

In 2009 a new version of Vampires Rock was created, called Vampires Rock Christmas, and Willcox was back in her role as the Killer Queen, alongside the Writer and one of the stars of the show, Steve Steinman. Willcox continued to perform with The Humans, featuring Bill Reiflin, Chris Wong and occasionally husband Robert Fripp. Described as "European experimental meets West Coast American grunge", The Humans recorded their debut album We Are the Humans in Seattle in 2008, released in Estonia in May 2009 to coincide with the band's return to play in front of the country's President. The album received a UK digital release in September 2009, along with a single "These Boots Are Made for Walkin'". At the end of the year Willcox came seventh in a BBC series naming the "Queens of British Pop", as voted for by the British public. In 2010 Willcox with The Humans performed at the London's Roundhouse Haiti earthquake fundraiser concert. On 17 June 2011, Willcox commenced on a special From Sheep Farming to Anthem tour, celebrating the 30th anniversary of her breakthrough hit "It's a Mystery" and the platinum-selling album Anthem, starting at the London's Leicester Square Theatre. The set included selections drawn exclusively from Toyah's first three albums, Sheep Farming in Barnet (1979), The Blue Meaning (1980) and Anthem (1981). Andi Fraggs, a British electronic musician, supported her on chosen dates.

On 14 April 2012, Willcox launched the Changeling Resurrection 2012 tour at the Concorde 2 in Brighton to celebrate the 30th anniversary of her album The Changeling (1982). On 16 July 2012, Willcox performed a concert in her birthplace of Kings Heath, Birmingham, to celebrate being the first Artist with a star on the King's Heath Walk of Fame. Andi Fraggs made a surprise appearance, duetting Willcox's 1981 hit single "Thunder in the Mountains". In 2013, Toyah released a deluxe edition of her 2008 album In the Court of the Crimson Queen and embarked on the tour revisiting the Love Is the Law (1983) -era material.