Henry debuted with the Super Junior Chinese sub-unit Super Junior-M on April 8, 2008 with the Chinese cover of the 2006 Super Junior song U. A few days later, they released their debut studio album Me, which won them Best Album at the CCTV 2008 Chinese Entertainment Awards. In June 2013, Henry released his debut solo extended play Trap in South Korea, which featured the singles Trap and 1-4-3 (I Love You). The Chinese version of the album was released in August 2013.

In February 2014, Henry became a cast member of the South Korean variety show Real Man, which earned him the Best Male Newcomer citation at the MBC Entertainment Awards. He then made his acting debut with a supporting role in the 2015 Mnet series Persevere Gu Hae-ra. In 2017, he joined the cast of the MBC reality show I Live Alone, which scored him an Excellence Award at the MBC Entertainment Awards. In 2018, he parted ways with his longtime agency SM Entertainment and established his personal studio in China. In 2019, he made his Hollywood debut with the family comedy-drama film A Dog’s Journey, which grossed more than $75 million worldwide. In 2021, he starred in the second season of the Korean-American series Dramaworld.

Henry’s father is of Teochew ancestry while his mother is Taiwanese. He has two siblings named Clinton and Whitney. He can speak multiple languages such as English, Mandarin, and Korean. He attended Berklee College of Music in Boston.