Born in Rochester, New York, Wang is the second of three sons of immigrants from Taiwan of waishengren heritage. His father, a pediatrician, and his mother, moved to the United States to further their college studies in the early 1960s. Influenced by his older brother, Leo Wang, who had been taking violin lessons since he was seven, Wang began to develop a curious interest towards the violin and its musical counterparts when he was three. He begged his mother to put him in violin lessons with his brother but his mother was against it, reasoning that he was too young. When Wang turned six, his mother enrolled him in violin classes, performing along with his brother. As he became a teenager, he began taking piano lessons, also teaching himself the guitar. He also worked several jobs to earn money to buy a second hand drum kit.

In the summer of 1995, while Wang was visiting his grandparents in Taiwan, he was offered a professional recording contract by Bertelsmann Music Group (BMG) after he participated in a talent competition hosted by the label. Not wanting to lose the opportunity, he immediately began preparing for his debut, and released his debut album Love Rival, Beethoven (情敌贝多芬) that December. The record received little limelight, forcing him to leave the label. He signed with Decca Records the following year, a label then famous for producing "powerful singers" (實力派歌手) in Taiwan. Wanting to also have control in the idol market, the label initially planned to market Wang as the mainstream "romantic idol", like with their previous Artist Mavis Fan. However, after discovering Wang's talent in music-making, Decca began promoting him as Taiwan's "quality idol" (優質偶像) instead. Wang released his second album If You Heard My Song in 1996, which included some of his own compositions. He co-wrote the album's eponymous title song, which earned positive responses from the audience. The album drew moderately successful sales, and he became a rising star in the idol market, also finding similar successes with his third and fourth albums. During this time, Wang was asked to leave his college studies to pursue a full-time singing career, but he insisted on finishing school first.

Wang's contract with Decca Records was terminated after the release of his fourth album White Paper in the summer of 1997. After graduating with honors at Williams College, he released his first award-winning album Revolution under Sony Music Entertainment in August 1998. The album became his breakthrough album, immediately selling over 10,000 domestic units in the first week of release. Critics rated the album highly, and it won Wang two Golden Melody Awards—Best Producer and Best Mandarin Male Singer. He was the youngest Artist to win in either of the two categories. Wang has been nominated the Best Mandarin Male Singer at the awards every year since the success of Revolution. The singles of Revolution also achieved similar success–"Revolution" became Wang Leehom's first No. 1 single, becoming one of the top 20 songs of the year on Channel V Taiwan.

Wang is one of the most highly visible celebrities in Asia due in no small part to his many product endorsements including: Coca-Cola, McDonald's, Sony Ericsson, Bausch & Lomb, Bosideng MAN, Garnier, Lay's Chips, Nikon, Brand's, Hyundai, and also Wahaha purified drinking water, which he has endorsed since 1999.

Wang had displayed interest in acting when he starred in several musical plays when he was in high school and college. In 2000, he made his feature film debut in the Hong Kong action crime thriller, China Strike Force, starring alongside Aaron Kwok, Norika Fujiwara, and Ruby Lin. Hong Kong critics had remarked Wang for giving a well-toned performance as his first film. His next starring role was the 2001 Hong Kong science fiction film The Avenging Fist as the main character Nova. He then starred in two Japanese films Moon Child (2003) and Starlit High Noon (2005).

Eager to experience and perform different musical genres, Wang embarked on his first Asia-wide concert tour The Unbelievable Tour a few months before the release of his ninth album Unbelievable (2003). His concert tour received great reviews from both fans and music critics; they were impressed and shocked with his new-found hip hop image. His R&B/hip hop-inspired album Unbelievable involved new urban pop numbers, drawing hip hop influences from different styles of popular music, such as Indipop and urban pop. The album marked a milestone in his musical career; his new image received international critical acclaim and the album a chart-topping success, selling over 1.5 million units by 2004. A celebratory version of the album was released three months later, also becoming a chart-topping album. The album's ballad "You're Not Here" also experienced international success, ranking No. 1 on several music charts for over 10 weeks. Unbelievable yielded his second win for Best Producer of the Year at the Golden Melody Awards in 2004.

Since 2004, Wang became known for his brand of China Wind music, known as "chinked-out". Having established himself as one of the most important, influential, and prolific artists in Chinese music, Wang continued to invent and experiment with new sounds and voices. For most of 2004, he traveled to remote villages in China, collecting often unheard tribal sounds of aboriginal Chinese music, Tibetan music, and Mongolian music. With his younger brother Leekai as his assistant, they carried 15 kg of music equipment as he recorded these sounds, recording and producing his album on the way. He incorporated these sounds into R&B and hip hop music, coining the style as "chinked-out." Despite the derogatory nature of the term "chink," Wang had wanted to repossess the term and "make it cool." Shangri-La was released on the last day of 2004, selling 40,000 copies within the first ten days of release. Shangri-La became an international music sensation, especially catching the attention of many youths in Asia. Within a month, the album sold over 300,000 copies, ultimately selling over 1.5 million units.

Wang continued to infuse chinked-out elements into his next album Heroes of Earth (2005). Unlike the aboriginal tribal music heard in Shangri-La, Heroes of Earth contained mixes of Beijing opera and Kunqu. Following the concept of "heroes," he collaborated with Ashin of Mayday ("Beside the Plum Blossoms"), Chinese American Rapper Jin and opera master Li Yan ("Heroes of Earth"), and also K-pop artists Rain and Lim Jeong-hee ("Perfect Interaction"). Heroes of Earth was the fastest-selling album of both 2005 and 2006, selling over 1 million copies ten days after its release. Subsequently, the album stayed as No. 1 in the charts for six weeks, and remained in the charts for 23 weeks, ultimately becoming 2006's third best-selling album. By 2007, about 3 million units were sold, and has since been Wang's most commercially and critically successful album. The album earned Wang a Golden Melody Award for Best Mandarin Male Singer for the second time.

Three months after the release of Heroes of Earth, he began the Heroes of Earth Tour, his first major world tour. The concert commenced with two shows per night in the Taipei Dome in March 2006, breaking Taiwan's concert attendance records.

The major breakthrough in his film career was in Lust, Caution, directed and produced by Academy Award-winner Ang Lee. The film is based on a novella written by Eileen Chang and revolves around a plot to assassinate a high-ranking Chinese official in the Wang Jingwei Government using a beautiful young woman as bait. Wang plays Kuang Yumin, a patriotic college student who persuades Wong Chia-chi (Tang Wei) to seduce Mr. Yee (Tony Leung). The film was released in the US cinemas on September 28, 2007. Lust, Caution was produced on a budget of approximately $15 million and grossed $64,574,876 worldwide.

Another reason he was chosen is due to Wang's enthusiasm in the 2008 Olympic Games Theme Songs Competition. His single "One World One Dream" was chosen as an Olympic Games participation song. The single was written, sung, produced, and scored entirely by himself. He sang along with Jackie Chan, Stephanie Sun, and Han Hong in the song for "The One Man Olympics" which was about the first Chinese to be in the Olympics. He also sang in the 100 days countdown theme song "Beijing Welcomes You". He also sang alongside Stefanie Sun, Wang Feng, and Jane Zhang in the Beijing 2008 Olympic Games Torch Relay theme song "Light the Passion, Share the Dream". He is also one of the candidates on vote for performer of the Beijing 2008 Olympic Games theme song. In the closing ceremony, he sang "Beijing Beijing, I Love Beijing" alongside Hong Kong singer Kelly Chen and Korean singer Rain.

In 2009, Wang was selected to star with Jackie Chan in Little Big Soldier.

In 2010, Wang stepped behind the camera to direct and star in, Love in Disguise (Chinese: 戀愛通告; pinyin: Liàn ài tōng gào), also starring Liu Yifei and Joan Chen. Love in Disguise went on to become the highest-grossing film for a first-time Director in Chinese history grossing over 60,000,000 RMB domestically.

On September 7, 2011, it was announced that Wang hired Wong Fu Productions to direct his upcoming music video.

Since 2012, Wang has been starting almost every year by holding a free show for his fans. The shows are usually held in an intimate setting with him and a small band in different cities every year, and tickets are given away free-of-charge on a first-come-first-served basis. The annual show has been held in the following cities:

On November 27, 2013, Wang married Taiwanese girlfriend, Lee Jing Lei. The couple has two daughters, Wang Jiali, born July 2014, and Wang Jiana, born October 2016.

Wang collaborated with Swedish EDM DJ Avicii for his 2014 single Lose Myself, which was the theme for the Storm Music Festival, China's biggest electronic music festival held on October 5 & 6, 2014 in Shanghai. The song is also the first single to be released from his 2015 album, Your Love.

Wang co-starred with Chris Hemsworth and Tang Wei in Blackhat (2015), an action thriller film on cybercrime which was written, directed and produced by Michael Mann.

Feb 27, 2017, Madame Toussauds revealed Wang's wax statue in their Beijing museum.