After graduating, Klass spent a short period as part of a reality show for Bravo, called The Dolls’ House. She sang backing vocals for Sir Cliff Richard, who she had previously worked alongside at aged 10 when she sang in a choir featured in his 1988 single Mistletoe and Wine, which was that year’s Christmas number one on the UK Singles Chart, and made her West End theatre debut in Miss Saigon. Her brother, Don Klass, is an actor.

Early television work came in 1998, when Klass sang Soprano for the music of the Channel 4 film Alice through the Looking Glass.

In 2001, Klass auditioned for the ITV reality show Popstars, which offered contestants an opportunity to become part of a newly formed pop band. Klass was chosen as one of the 10 finalists and became a member of Hear’Say, alongside Kym Marsh, Suzanne Shaw, Danny Foster and Noel Sullivan. Following the success of their first album, the band was given their own TV show entitled Hear’Say It’s Saturday. During the show’s run, the band had a chance to perform with such established artists as Lionel Richie, Celine Dion, Bradley Walsh, Blue and Atomic Kitten. At the end of 2001, Hear’Say appeared on the Royal Variety Performance.

Subsequently, the group achieved a 37-date sold-out arena tour and performed numerous television guest appearances. Klass made many appearances with Hear’Say on TV and in live performances during 2002. The pop act’s many promotional appearances during the year were also broadcast as part of their own TV shows, entitled Hear’Say: A New Chapter in Full and The Hear’Say Story. In total, Hear’Say had four Top 10 singles including two number-ones in the British charts, before splitting after a reported long-term feud between Klass and Marsh. The feud resulted in Marsh leaving the band in December 2001, to be replaced by Johnny Shentall in 2002. Unfortunately the band split up in October of that year.

Almost a year after Hear’Say’s break-up on 13 May 2003, Klass signed a five-album deal with Universal Classics and Jazz. Promotion started with the release of the main promotional single “Toccata and Fugue” to TV channels and was the first ever classical piece to appear on British music television channel The Box. She also appeared in the video for “Da Ya Think I’m Sexy?” with The Girls of FHM, which went to No. 10 in the UK Singles Chart.

Klass’s album, entitled Moving On, was launched on 20 October 2003 at Harrods, London. The album included reworked versions of popular classical pieces such as Fauré’s Pavane, Beethoven’s Moonlight Sonata and Satie’s Gymnopedie No.2. Moving On also included music from Oscar-winning films Gladiator and The Piano. New arrangements for piano of more contemporary works were also included on the album, namely Linkin Park’s “Crawling” and Daniel Bedingfield’s “If You’re Not the One”. In its first week of release Moving On peaked at No. 2 in the UK Classical Chart, behind Hayley Westenra. It peaked at No. 32 in the UK Albums Chart. By mid December 2003, the album had been certified gold. In April 2004, Moving On was nominated as Album of the Year in the Classical BRIT Awards. The award went to Bryn Terfel’s platinum-selling record Bryn.

Klass confirmed there would be a re-release of the album featuring five new tracks, however its release was pushed back because of conflicts between Klass’s new management company (Mel Bush Organisation) and her previous (Safe Management) regarding royalties. Ultimately the release was cancelled, the only remnant being the Asian release of Moving On, which includes three new tracks: “Trouble” (a Coldplay cover with Klass’s vocals), “Sahara”, and “Le Onde”. Klass then revealed that she would be working on a new album, which would include a number of tracks featuring her vocals. However, on 23 October 2004 it was announced that Klass would not be releasing any further material through her label UCJ, Universal Classics and Jazz.

In November 2004, Klass posed for Loaded magazine. After she appeared in a shot for Maxim magazine in February 2006, it was revealed in April 2006 that Klass charted at number 78 in the FHM 100 Sexiest Women of 2006, after not being included the previous year. She had previously been featured at number 84 in 2002, number 33 in 2003 and 43 in 2004. Klass was chosen as the new face of Ortak Jewellery. In January 2007, it was announced that Klass had signed a multimillion-pound deal with Marks & Spencer to model clothes and swimwear for the new season. As the new face and body of Marks & Spencer’s Spring and Summer Collection, Klass appeared in both print and television advertising, including one modelled on Ursula Andress’s first appearance in Dr. No. From 2012, Klass modelled for catalogue store Littlewoods.

In August 2005, Klass was signed as a presenter for the ITV music show CD:UK alongside Lauren Laverne and Johny P, with her first appearance shown on 17 September 2005. In 2005, Klass appeared as a guest panellist on the topical discussion show The Wright Stuff on a number of occasions. During Christmas 2005, Klass appeared on a celebrity version of the BBC’s quiz show Mastermind.

In December 2005, Klass was attacked by a group of teenagers in a newsagent in Bermondsey. Klass had a bag of chips dropped on her head, and was pushed to the ground. The teenagers attempted to take photos of Klass on their mobile phones.

At the Cathedral Church of St John the Baptist, Norwich on 24 June 2005, Klass performed a selection of tracks from her Moving On album, as well as accompanying some local schoolchildren in a concert of classical standards. The cathedral summer concert was organised to raise funds for an extension of the church building. Part of this performance was recorded by MTV, who were following Klass at the time for a show called The Price of Fame. The programme was later broadcast by VH1 and also by ITV, where it was only shown in the London region. The recording by the music channel was acknowledged by Klass during the evening.

On 6 August 2006, Klass was a guest reporter on BBC One’s popular Sunday morning religion and ethics show Heaven & Earth with Gloria Hunniford. Klass’s report, billed as the feature of the week, was on the Pope’s astronomer. From 10 October 2006, Klass co-presented LIVINGtv’s Ghost Towns beside popular medium and ex-Most Haunted star Derek Acorah. In May 2007, Klass appeared on Sky HD’s Test Card.

Klass took part in the sixth series of ITV’s reality television series I’m a Celebrity…Get Me Out of Here!, which began on 13 November 2006 and ended on 1 December 2006. She finished in second place, behind Matt Willis. Klass’s brother Don, noticing his sister’s popularity with the male audience, suggested she auction off her now famous bikinis from the show on eBay. Within a week of leaving the jungle, Klass took his advice and put her white bikini from the show on auction on eBay until 7 December 2006. Klass pledged that all the money raised from the auction would go to charity to help victims of the Farepak savings scandal. The auction raised £7,500.

In February 2006, Klass began presenting the Sunday Breakfast programme on Classic FM, taking over from Aled Jones (who returned to this slot in 2016). She worked for several years on the station’s early morning show on Saturdays and Sundays and currently presents the Saturday and Sunday evening Smooth Classics programme (10 pm – 1 am). While working on the weekend morning show for Classic FM, she was also heard on London’s Capital Radio on Sunday evenings from 8 to 10 pm. This show was also broadcast on GCap Media’s One Network local commercial radio stations around the UK.

In early 2006, Klass was cast as one of the three women starring in the long-running play The Vagina Monologues and performed in Bromley, Richmond and Brighton. Her run was then extended to include all dates in Nottingham. Olympic champions joined Klass on 13 December 2006 to launch Lucky Dog, a new London 2012 National Lottery scratchcard. In 2008 Klass began designing a range of baby clothes for Mothercare called Baby K. Klass also writes a regular blog for the pregnancy and parenting website Gurgle, which is owned by Mothercare. Klass is the official godmother of the cruise ship Carnival Splendor. Klass is an EDF Energy / Team Green Britain Ambassador and took part in the launch of the EDF London Eye on 27 January 2011. In 2011, Myleene Klass began working with children’s shoe brand Start-rite, helping the company design and promote a range of fitted footwear.

In May 2006, Klass was involved in a go-karting crash at a charity race in Cardiff, South Wales, sustaining an injury to her leg.

Klass has been an amateur astronomer for most of her life, having been taught the basics by her father. She was one of a handful of celebrities, engineers and scientists who were at the UK National Space Centre control centre for the touchdown of the UK Mars probe Beagle 2 in the early morning of Christmas Day 2003. Since then she has been a keen supporter of the UK’s work in the European space programme. In March 2006, Klass publicly criticised the proposed closure of the London Planetarium and explained on television how to view Venus in the early morning. She also appeared on Channel 4’s Richard & Judy to discuss the book Moondust, which follows the lives of the first men on the moon, and in 2007 attended the televised party on BBC One, held at the home of Patrick Moore in Selsey to mark the 50th anniversary of Moore’s monthly programme, The Sky at Night. Klass once studied astronomy with the Open University.

On 15 July 2006, as part of BBC One’s Sport Relief charity spectacular, Klass appeared as a special guest in the Question of Sport Relief segment. Klass’s appearance involved her playing a variety of TV sport theme tunes on a grand piano. This part of the fundraiser was based on the BBC’s popular A Question of Sport quiz show and was hosted by Sue Barker. Guest panellists on the show included Nancy Dell’Olio and Zara Phillips, who played alongside the regular team captains Ally McCoist and Matt Dawson.

During December 2006, Klass also appeared on The Big Finish with Graham Norton, in which she competed alongside Bill Oddie and Big Brother star Nikki Grahame for the “Showbiz” team (against “Soap” “Sport” “News” and “Judges” teams) to compete to win £10,000 for the winning team’s chosen charities. However, the Showbiz team, represented by Graham in the final round, was beaten by the Soap team represented by former EastEnders actress Wendy Richard. In November 2007, Klass guest-presented BBC Children in Need and performed Your Song with John Barrowman. She also collaborates with Norwood, a Jewish charity for children.

On 28 March 2007, Klass signed a record contract with EMI Classics as both a recording artist and an ambassador for the EMI Classics UK roster of artists. These include Alfie Boe, Natasha Marsh and Natalie Clein. The deal includes the release of a series of albums on which Klass performs two exclusive tracks and chooses a number of her favourite classical pieces from the EMI Classics back catalogue. The first album, Myleene’s Music for Romance, was released on 2 July 2007 and went straight to number 1 in the classical chart. A music video to accompany the lead track “Cinema Paradiso” was shot at the Bucharest Opera House, Romania in April.

From July – August 2007 Klass co-presented the daily BBC One programme The One Show with Adrian Chiles, before quitting to concentrate on looking after her baby. On 31 December 2007, Klass presented the BBC One programme, New Year Live, for the countdown to the year 2008 at midnight.

On 1 April 2007 she announced she was pregnant, with her first child due on 7 September. As a result, she delayed her wedding to Graham Quinn until 2008. Their daughter Ava was born on 16 August 2007. Klass’s spokesman said: “Myleene presented The One Show and felt a bit weird on the way home. She went to the hospital to get checked out and they told her she was in labour”.

Klass’s second album in the EMI series, Myleene’s Music for Mothers, was released on 18 February 2008, and features two tracks played by Klass. These two tracks are the popular “America” from West Side Story, written by Leonard Bernstein, and Ennio Morricone’s “Chi Mai”, known best as the theme to the 1981 BBC TV drama serial The Life and Times of Lloyd George.

On 27 May 2008 Klass presented the BBC Radio 2 show Friday Night is Music Night in front of a live audience at the Watford Colosseum, Watford, Hertfordshire. The recording of this show was broadcast on 18 July 2008. In 2008 Klass presented various shows on TalkRADIO, filling in for James Whale and Jon Gaunt.

She also co-hosted the American version of I’m a Celebrity… Get Me out of Here! in 2009 on NBC.

In January 2010, Klass claimed she received a warning from Hertfordshire Police for brandishing a kitchen knife (through a window) at a group of teenagers who entered her garden while she and her daughter were alone in the house – she stated she was “utterly terrified” and “aghast” at the response by the police. Hertfordshire Police have denied making any such warning and stated that the law allows householders the proportionate use of force to protect themselves. It has subsequently been reported that it was Klass’s agent or publicist who notified the police of the incident and who then passed on the story to The Sun’s reporter, Emma Cox.

Klass published a book about her experiences of being pregnant, entitled My Bump and Me: From Morning Sickness to Motherhood – An Honest Diary of My Pregnancy. Klass gave birth to a second daughter on 25 March 2011. On 21 October 2011, Klass and Quinn married, with 16 people in attendance. On 23 April 2013, Klass was granted a divorce.

In March 2013, she helped to celebrate Andrew Lloyd Webber’s 40-year work with her rendition of “Shakalaka- Baby” from the musical Bombay Dreams.

In November 2014, Klass caused controversy by engaging in a heated debate with then-leader of the Labour Party, Ed Miliband, on the ITV show The Agenda. Discussing his proposals for a so-called mansion tax on larger homes, Klass expressed the view that this would hit “little grannies”. In the course of discussion, she pointed to a glass of water, saying “You can’t just point at things and tax them.” The row later featured in an attack on Miliband by Prime Minister David Cameron at Prime Minister’s Questions.

Klass began presenting a Saturday drive-time show on Smooth Radio in 2014. Klass presents the weekday 10AM-1PM Slot covering for Kate Garraway while she is looking after her husband who has Coronavirus. Garraway returned to the mid morning show on 14th September and Klass returned to her usual Saturday Drive-time show.

In 2015, Klass began presenting the new ITV series BBQ Champ, beginning on 31 July.

On 1 March 2018, Klass hosted The Global Awards 2018 alongside Rochelle Humes and Roman Kemp

On 1 August 2019, she gave birth to her third child, a boy named Apollo.

On 20 September 2020, it was announced that Klass would be a contestant on the thirteenth series of Dancing on Ice. She was paired with Łukasz Różycki.