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.

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 North West China's Qinghai province.

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.

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.

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.

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.