At age 11, in 1988, she moved with her parents from Hong Kong to Montreal, Canada. Ho first attended Jean-de-la-Mennais College, an elementary and middle in La Prairie, on the South Shore of Montreal, then attended Collège Jean-de-Brébeuf, a Catholic college preparatory secondary school and private college. There, she received a Quebec Diploma of College Studies in Arts and Communications.

In 1996, she returned to Hong Kong to take part in the New Talent Singing Awards (NTSA). Afterwards, she began her studies at Université du Québec à Montréal (UQAM), in graphic design. She had only studied the degree for a semester before returning to Hong Kong to kickstart her career.

Ho released her first album “First” in 2001, in her fourth year of the contract with Capital Artists. Produced by Choy Yat Chi of Grasshopper (band), this EP, containing her first single “Thousands More of Me” (千千萬萬個我) and “Home of Glory” (光榮之家), defined with success Ho’s style as the rock pop independent female she is up till recent years. She earned the award of “Best New Singer” in various prize presentation ceremonies that year. In October, Capital Artists announced bankruptcy, resulting in the end of Ho’s first record label era.

After Capital Artists closed, Ho joined EMI in 2002. Although she was only with the company for a brief 2-year period, it was during this time that her musical talents flourished. She teamed up with Ying C Foo (英師傅) for her first EMI label release, Hocc². The song “Angel Blues” (天使藍), composed by Ho herself, not only reached top spots on music charts, but according to Ho, it is also her “growing up” song.

In 2002, Ho’s two singles “Angel Blues” (天使藍) and “Goodbye… Rosemary” (再見…露絲瑪莉) won multiple music awards in Hong Kong, including CASH Golden Sail Music Awards (CASH金帆音樂獎) – “Best Vocal Performance by a Female Artist” for the song “Angel Blues”. In the same year, Ho won the renowned “Female Singer Bronze Award” in the Ultimate Song Chart Awards Presentation (叱吒樂壇流行榜頒獎典禮).

In 2003, Ho held a “Music is Live” concert with Andy Hui, who is also an apprentice of Anita Mui. Their performance won praise from the critics, and Ho proved to the audience her abilities to perform live as a musician. Later that year, Ho released her second full-length album “Dress Me Up!”. She was the credited as the producer of the album, indicating that Ho has finally gained full control over her music. In September 2003, Ho’s longtime mentor, Anita Mui announced she was diagnosed with cervical cancer. Shortly after the announcement, Anita lost her battle against cervical cancer and died on 30 December 2003.

Between 2003 and 2004, Ho took on the role of hosting TVB’s weekly live music show, Jade Solid Gold. In 2004, she appeared in Sammi Cheng’s 2004 “Sammi vs. Sammi” concert as a cross-dressing cigarette-smoking admirer of Sammi Cheng. Ho’s critically acclaimed performance in the short musical segment not only brought attention to the role she played, but also further established herself as a tremendous live performer. In September 2004, Ho signed a contract with East Asia Music.

The album “Glamorous”, which pays tribute to the superstars of the 80s, was released in January 2005. It also marked the start of a close collaboration between Ho and the Green Mountain Orchestra band. She was named the Orbis Student Ambassador 2005, and visited Hainan in July. In September 2005, Ho performed in the musical Butterfly Lovers (梁祝下世傳奇) as the leading actress, producer and musical director. Her album of the same name gave her three Number 1 singles – “Becoming a Butterfly” (化蝶), “Lawrence and Lewis” (勞斯．萊斯) and “Coffee in a Soda Bottle” (汽水樽裡的咖啡), which are all based on the story of the Butterfly Lovers, with possible homosexual themes. These singles helped her to receive the “Female Singer Silver Award” at the Ultimate Song Chart Awards Presentation 2005 (叱吒樂壇流行榜頒獎典禮).

Ho held her first Hong Kong Coliseum concert “Live in Unity 2006” on 26–28 October 2006. The concert was a great success and was positively received by the public. She decided to stage a second concert, “Live in Unity 2007”, on 19–20 January 2007 following the original concert’s success. Her single, “We Stand As One”, named after the slogan for the “Live in Unity” concerts, was released on 11 January 2007. Recordings of the concert were later released in February 2007. She went on a worldwide tour, performing in Toronto, Canada and Atlantic City, New Jersey.

The significant public attention and positive reception to her music helped her garner the “Female Singer Gold Award” at the Ultimate Song Chart Awards Presentation 2006 (叱吒樂壇流行榜頒獎典禮). She sang the Chinese version of Ayumi Hamasaki’s song “Secret”, known as “Wounded City Secret” (傷城秘密), for the 2006 movie Confession of Pain. She continued as the Orbis Student Ambassador 2006 and visited Vietnam, and later started her own charitable fund. In 2008, a new album “Ten Days in the Madhouse” was released. She produced this album from the viewpoint of society’s outcasts and to raise awareness of mental health issues. She encouraged people to understand and find out more about people with mental illnesses and those who formerly suffered from mental illnesses, and care about their needs and situations. Ho encouraged communication between them and the public, ultimately, to achieve social harmony. “Ten Days in the Madhouse” was Ho’s most ambitious project. Yet, with the release of a documentary by Hong Kong director Yan Yan Mak (Butterfly) and an exhibition for charity, Ho showed that a multimedia project by a musician can be about something more important than clothing tie-ins.

In 2009, she followed up her plan from the previous year and organised a free concert called “Happiness is Free” in the outdoor courtyard of Diocesan Boys’ School. She managed to book the place because her father was a teacher there. In June, she began shooting a new TVB sitcom titled O.L. Supreme with Liza Wang. In July, she released her new song “The Old Testament” (舊約) and announced that she would hold her “SUPERGOO” themed concerts from 9–12 October that year. Following the concerts, Ho took on a role in the new stage comedy “Man and Woman, War and Peace” (男人與女人之戰爭與和平) directed by Edward Lam. The stage comedy was presented on 13–16 November at Kwai Tsing Theatre in Hong Kong.

In 2010, Ho appeared in the film Life Without Principle directed by Johnnie To. In September 2010, her first Mandarin album “Nameless Poem” (無名．詩) was released in Taiwan and Hong Kong, and she held “Homecoming” concerts in Hong Kong in December 2010. In 2011, Ho received her first nomination in the 22nd Golden Melody Awards as “Best Mandarin Female Singer”.

In 2012, she was nominated in the 49th Golden Horse Award for “Best Actress” for her performance in the movie “Life Without Principle”. In the same year, she came out as gay at the fourth annual Hong Kong Pride Parade, becoming the first “mainstream female singer in Hong Kong to come out of the closet”. Since then, Ho has been actively involved in striving for LGBT rights.

Ho proudly announced herself as “tongzhi” (Cantonese:tongzi), a Chinese slang term for gay, at age 35, at the fourth annual Hong Kong Pride Parade on 10 November 2012.

In 2013, Ho continued the tour of her play, “Awakening”, in Singapore and in many cities in China. She released her second Mandarin album, “Coexistence”, which touches upon the theme of loving others despite differences. Ho received her second nomination in the 25th Golden Melody Awards as “Best Mandarin Female Singer” in 2014.

In 2014, Ho made her stance clear when police fired tear gas in a futile attempt to disperse thousands of mostly-young pro-democracy protesters who had taken to the streets for the “Umbrella Movement”.

In March 2015, Ho’s contract with Media Asia Music (previously named as East Asia Music) expired. She announced in her Facebook and newspaper column in Apple Daily that she would become an independent artist. Afterwards, she organized multiple events on her own: “Reimagine Live”, a self-funded concert in Taiwan, and a local charity market co-organized with Nomad Nomad. On 19–24 August 2015, she also held a self-funded concert “Reimagine HK18” in Hong Kong Queen Elizabeth Stadium.

On 7–10 October 2016, Ho returned to the Hong Kong Coliseum for her first crowdfunded concert “Dear Friend,”. As she was banned and blacklisted by China, Ho could not find any powerful sponsor that would support her shows. So she came up with a crowdfunding alternative she called “Togetherly Exclusive.” She invited individuals and small and medium enterprises to pledge sponsorship for the event. Eventually, sponsored by over 300 small enterprises and individuals, the four-day concert was successfully held and revisited 24 of the singer’s greatest hits.

On 5 June 2016, French cosmetics brand Lancôme cancelled a promotional concert by Denise Ho that was scheduled to be held on 19 June in Sheung Wan. This action was taken in response to a boycott campaign launched by the Communist Party-controlled Global Times, which denigrated her for supposedly supporting Hong Kong and Tibet independence.

In May 2018, Ho published a new song “Polar”, marking her first attempt to write lyrics for a song. In September, Ho collaborated with Taiwanese band Chthonic on their song Millennia’s Faith Undone, which required her to sing in Taiwanese Hokkien. Later, an acoustic version of the song was also released.

Ho faced a visa refusal by Malaysia in February 2018, which forced her to cancel the concert on April, allegedly related to her stance on LGBT and her LGBT identity.

In 2019, Ho started to become an active speaker in international human rights forum. In May 2019, Ho was invited to participate in Oslo Freedom Forum. She made a speech on the topic “Under the umbrella : Creative dissent in Hong Kong” and performed “Polar” to the audience. Followed by that is Hong Kong’s anti-extradition law amendment bill protests. Ho, as a Canto-pop star turned activist, got worldwide media coverage due to her active participation in the movement. On 8 July, she attended the United Nations Human Rights Council’s meeting in Geneva. During her short speech, she called on the council to remove China from the body and convene an urgent session to protect Hongkongers, sparking two interruptions by Chinese delegate Dai Demao. On 20 August, Ho participated in Singularity University’s (SU) annual Global Summit and did a keynote speech about how Hong Kong people utilize technology in their social movements.

In 2019, Ho became an active speaker in international human rights forum. In May 2019, Ho was invited to participate in Oslo Freedom Forum, a global platform for human rights defenders to share their stories. She made a speech on the topic “Under the umbrella : Creative dissent in Hong Kong” and performed “Polar” to the audience.

Ho has received numerous awards. As a solo artist she has achieved IFPI’s “Top 10 Best-selling Local Artists Award” for 9 consecutive years, making her one of the best-selling artists in Hong Kong. She had also won the title of “Best Female Singer” and “My Favourite Female Singer” in the CRHK Ultimate Song Chart Awards Presentation over the past years, securing her position as a leading pop diva in the city. In recent years, although she is blacklisted by China, she has started up her own record label and continued to produce music. In 2019, she has collaborated with CHTHONIC, a Taiwanese band, to make the song “Millennia’s Faith Undone”. The song is nominated as “Song of the Year” in the 30th Golden Melody Awards.

A 90-minute documentary film produced by Sue Williams, Denise Ho: Becoming the Song, released on 1 July 2020 in solidarity with the protest, marks the 23rd anniversary of Britain’s handover of Hong Kong to China in 1997.