He is best known for his leading roles in the films Volcano High (2001), Windstruck (2004), The Flu (2013), as well as the television series Successful Story of a Bright Girl (2002), Thank You (2007), The Slave Hunters (2010), Deep Rooted Tree (2011), You Are My Destiny (2014), Voice (2017), Money Flower (2017–18), and Bloody Heart (2022).

[2] After Lee Seung-hwan's music video, Jung Yong-joon making his acting debut in 1997 in the television drama Model under his stage name Jang hyuk.

Besides the teen series School (1999) and a minor role in the little-seen film Zzang (The Best),[3] Jang appeared in the music video of "To Mother", the 1999 debut single of popular boyband g.o.d, whom he was housemates with at that time.

[11][12] He also took a role in Public Toilet, the HK-Korea co-production by acclaimed Hong Kong director Fruit Chan which won a Special Mention in the Upstream section of the 2002 Venice Film Festival.

[21] A heartwarming story about a young single mother (played by Gong Hyo-jin) with an HIV-positive daughter and the cynical doctor who enters their lives, Thank You surprisingly became a modest hit, and with it Jang left the stigma of his draft-dodging scandal behind him.

After his earlier guesting on star Tsuyoshi Kusanagi's talk show, the director of the drama reportedly added new scenes for Jang that were not included in the original script.

[43][44] He next starred in legal thriller The Client (2011) with Ha Jung-woo and Park Hee-soon, saying the film satisfied his wish to portray a more emotionally complex persona.

"[45] Initially reluctant to sign on to period drama Deep Rooted Tree (2011) because he found the role of low-level royal guard Kang Chae-yoon uninteresting in the original novel, Jang changed his mind upon reading that the character had been dramatized and made richer in the TV script.

It tells the story of Kang investigating a case involving the serial murders of Jiphyeonjeon scholars in Gyeongbok Palace while King Sejong (played by Han Suk-kyu) is developing the Korean alphabet.

[52][53] He also returned to the big screen in 2013 blockbuster disaster film The Flu, in which he and Soo Ae played a firefighter and a doctor racing against time to find the cure for a deadly strain of the cold virus.

[54][55] To the surprise of many given his past draft-dodging scandal, he then joined Real Men, a weekly show in which six male celebrities are filmed documentary-style as they enter army boot camp.

[60][61] He also teamed up again with Successful Story of a Bright Girl costar Jang Na-ra in You Are My Destiny, a Korean remake of the similarly titled 2008 Taiwanese drama.

[65] In 2015, Jang returned to the milieu of period dramas with Shine or Go Crazy, a fictional romance between a cursed Goryeo prince and the last princess of Balhae.

[73] In 2017, he starred in his first cable drama, crime thriller Voice by OCN, where he played an ex-detective who joined a call center's team to track his wife's killer.

[76] His movie Ordinary Person opposite Son Hyun-joo was released in March 2017, where he acted as a manipulative National Planning Security chief.

[77][78] He also starred in weekend drama Money Flower,[79] earning much acclaim and a Baeksang Arts Awards Best Actor nomination for his role as a revenge-seeking lawyer.

In 2022, Jang returned to the small screen with KBS2's historical drama Bloody Heart, playing the first vice-premier and a living symbol of power and a figure that everyone obeys.

In January 2025, it was announced that Jang will make his directional debut with action film 'Stop Stop Dark Cold', in a partnership with a Hollywood-based production team.