Huang was born in Qingdao, Shandong and is an only child. His father was an engineer while his mother was an accountant. At age nine, he was selected by a film studio to play the child protagonist in a movie. Throughout his school life, Huang planned to become a scientist, but his language teacher encouraged him to apply to the Beijing Film Academy, which infrequently came to Qingdao to recruit students. A week before his entrance examination, his foot was ran over and crushed by a jeep; luckily, the injury was not serious because he was wearing army boots. While studying at the Beijing Film Academy, Huang recalls the person who had the greatest influence on him, a teacher named Cui Xinqin. He was close friends and classmates with Zhao Wei and Chen Kun; the trio was known as the "Three Musketeers".
In 1984, Huang was initially chosen by a producer to star in a drama as a child actor, but was dropped later because of his shy and introverted personality. In 1996, Huang auditioned for Beijing Film Academy and joined in the same year. He later debuted in the 1998 drama Love is Not a Game.
Huang began to gain attention when he was chosen to replace Lu Yi for the leading role in The Prince of Han Dynasty, which earned high ratings. He later starred in all three installments of the series from 2001 to 2005, and went from an unknown newbie to a front-line actor. He also played Tang Bohu in the drama Merry Wanderer Tang Bohu (2003), for which he won the Outstanding Actor award at the 14th Zhejiang TV Peony Award for his performance; and Xiao Jian in My Fair Princess III (2003).
Huang was chosen to play Yang Guo, the leading role in the 2006 television adaptation of Jin Yong's The Return of the Condor Heroes. Director Zhang Jizhong selected him over acclaimed actors Nie Yuan and Huang Jue to play the highly fought-over role.
Huang's most controversial and difficult, but most critically acclaimed role was in Shanghai Bund (2007), a remake of the 1980 Hong Kong television series The Bund, which starred Chow Yun-fat. Because Chow was his idol, he felt nervous, excited, and pressured about portraying the same role his idol had. In order to play Xu Wenqiang, he had to learn to smoke, and went through several packs a day. The series reported high audience ratings was voted as the most popular TV series in a survey on popular web portal Sina.com. For the role, Huang received Best Actor nominations at the 13th Shanghai Television Festival.
After achieving success in television, Huang decided to focus his career on the big screen. He challenged the role of a Japanese spy in espoinage thriller The Message, and won the Students' Choice Award for Favorite Actor at the Beijing College Student Film Festival. He also starred in the Hong Kong action film The Sniper (2009), martial arts film Ip Man 2 (2010) and the historical epic Sacrifice (2010) directed by Chen Kaige.
Huang made a comeback to television with Taiwanese idol drama Summer's Desire (2011), based on the novel of the same name by Ming Xiaoxi. Although originally slated to play Ou Chen, Huang asked if he could play Luo Xi instead. Huang later admitted that he lowered his acting fee in order to participate in this series.
Huang then took part in the production of An Inaccurate Memoir (2012), where he also starred as the male lead. His performance as a bandit leader who can’t see further than making money from plunder and kidnapping won him the Best Actor award at the 4th China Image Film Festival. Huang also starred in martial arts epic The Guillotines and played the younger version of Chow Yun-fat's character in The Last Tycoon.
The same year, Huang was selected as the ambassador of the Changchun Film Festival. He also became the first mainland actor to have his wax figure displayed in Hong Kong's Madam Tussauds museum.
Huang starred in the film American Dreams in China (2013) by Peter Chan. The success of the film brought a new impetus into Huang's career, and won him the Best Actor award at the 29th Golden Rooster Awards, 15th Huabiao Awards, 12th Changchun Film Festival and 32nd Hundred Flowers Awards. The same year Huang starred in another television project, playing the titular hero in the historical drama The Patriot Yue Fei.
Huang next starred in John Woo's The Crossing (2014). Set in 1930s Shanghai, the romantic epic is based on the true story of the Taiping steamer collision and follows six characters and their intertwining love stories; Huang plays a successful general who romances a wealthy debutante (played by Korean actress Song Hye-kyo). Another romance film followed; where Huang starred next to Fan Bingbing in The White Haired Witch of Lunar Kingdom, adapted from Baifa Monü Zhuan.
Huang returned to TV in the period romance drama, Cruel Romance (2015). The series was commercially successful, and recorded high ratings. The same year, Huang starred alongside long-time friend Zhao Wei in the action comedy film Hollywood Adventures. They became the first actors to be honored at Hollywood's TCL Chinese Theatre.
Huang then played Xuanzang in the historical epic of the same name in 2016, which tells the story of the monk's pilgrimage journey alone to India seeking Buddhist scriptures during the Tang Dynasty. The film was selected as China's entry for the Oscars under the Best Foreign Language Film category. Huang won several Best Actor trophies for his performance in the film.
Huang is a shareholder of Huayi Brothers Media Corporation, with about 1.8 million shares.
In 2009, Huang donated one million yuan to adopt two panda cubs and was named an ambassador to China's Panda Protection Research Center.
In 2010, Huang donated 200,000 yuan for earthquake relief to support for victims of the Yushu temblor in Northwest China's Qinghai province.
In 2016, Huang was named a UNAIDS National Goodwill Ambassador for China. The same year, he was appointed as an advocate for anti-trafficking by the Ministry of Public Security.
On Feb 28th, 2014, Huang announced his relationship with Angelababy. They registered their marriage with Qingdao Civil Affairs Authority on May 27, 2015 and on October of the same year, they had their wedding at Shanghai Exhibition Centre. On their 1st year anniversary, Huang announced Angelababy's pregnancy on Weibo. Their son was born on the 17 January 2017 in Hong Kong.
Huang is a friend of Zhao Wei, and he had told the media that while studying at the Beijing Film Academy, he had a big crush on her. They had remained close friends since then. In 2013, Huang showed up on crutches to help promote Zhao's directorial debut So Young. He described his friendship with Zhao as a fourth type of love - "Everyone needs a soulmate and I am lucky to have met mine in Zhao Wei".