Choi Min-sik was born on January 22, 1962 in Seoul, South Korea. When he was in third grade, Choi was diagnosed with tuberculosis and told by his doctor that there was nothing that could be done for him. Refusing to give up, he has eventually restored his health through an extended stay in the mountains.

Graduating with a degree in Theatre from Dongguk University, Choi first made a name for himself on the stage before breaking into the film world with roles in Park Jong-won's early films Kuro Arirang and the acclaimed Our Twisted Hero. In the mid-nineties he continued to act in theater productions as well as in several TV dramas, including The Moon of Seoul with Han Suk-kyu.

1997 marked his return to motion pictures, with a role as a tough-talking police investigator in Song Neung-han's No. 3. After a turn in Kim Ji-woon's debut film The Quiet Family, Choi's breakthrough would come in 1999, when he was cast in the record-breaking Shiri. His portrayal of a North Korean agent garnered him much praise and a Best Actor award from the 1999 domestic Grand Bell Awards. After starring in a theater production of Hamlet in the spring of 1999, Choi took on his first lead role as a husband who discovers his wife's infidelity in Happy End, and in early 2001 starred as a third-rate gangster opposite Hong Kong actress Cecilia Cheung in the cult melodrama Failan.

In 2002, Choi took on his most high-profile role yet in Im Kwon-taek's Chihwaseon ("Strokes of fire"), where he played the famous nineteenth-century Korean painter Jang Seung-up. The film won a Best Director prize at the 2002 Cannes Film Festival. Two years later, Choi would be back at Cannes with Oldboy, Park Chan-wook's Grand Prix-winning story of a man locked up for 15 years without knowing the reason why. Choi's impassioned and cool acting in Oldboy caused his popularity in Korea to soar, and made his name known to many overseas viewers.

He continued displaying his versatility in 2004 and 2005, playing a trumpet player who agrees to teach a school music class in Springtime, a down-and-out former boxer who struggles to put his life back together in Ryoo Seung-wan's Crying Fist, and a child murderer in Sympathy for Lady Vengeance, the last film in Park Chan-wook's revenge trilogy.

In 2005 he and Song Kang-ho were accused by director and Cinema Service head Kang Woo-suk of upping guarantees for high-profile actors, though Kang later rescinded the statement and apologized.

At various points during 2006, Choi (and other Korean film industry professionals, together and separately from Choi) demonstrated in Seoul and at the Cannes Film Festival against the South Korean administration's decision to reduce the Screen Quotas from 146 to 73 days as part of the Free Trade Agreement with the US. As a sign of protest, Choi returned the prestigious Okgwan Order of Cultural Merit which had been awarded to him, saying, "To halve the screen quota is tantamount to a death sentence for Korean film. This medal, once a symbol of pride, is now nothing more than a sign of disgrace, and it is with a heavy heart that I must return it."

In the next four years, Choi went on a self-imposed exile from making films, begun in protest over the screen quota but also partly due to the studios' reluctance to hire the outspoken and politically active actor. Instead he returned to his theater roots in the 2007 staging of The Pillowman, his first play in seven years.

During the retrospective on Choi held at the 14th Lyon Asian Film Festival in November 2008, the actor was asked his reaction to the upcoming remake of Oldboy, and he admitted to the French reporters present that he was upset at Hollywood for using what he described as low-style pressure tactics on Asian and European filmmakers so they could remake foreign movies in the United States.

Feeling a renewed passion for acting, Choi made his comeback in Jeon Soo-il's 2009 art film Himalaya, Where the Wind Dwells, in which he was the only Korean actor working with locally cast Tibetan actors.

Though Kim Ji-woon's 2010 thriller I Saw the Devil drew criticism from some quarters for its ultra-violent content, reviewers agreed that Choi's performance as a serial killer was memorable.

He did voice acting for Leafie, A Hen into the Wild, which in 2011 became the highest grossing Korean animated film in history. In his 2012 follow-up Nameless Gangster, Choi essayed another complex, layered antihero, and the Yoon Jong-bin film was both a critical and box office hit.

Choi's next film was Park Hoon-jung's New World, a 2013 noir about an undercover cop in the world of gangsters, which also became successful critically and commercially. Choi plays Yi Sun-sin in the upcoming period epic Battle of Myeongryang, about the titular battle regarded as one of the admiral's most remarkable naval victories.

For his English-language debut, Choi has been cast in Luc Besson's Lucy, which stars Scarlett Johansson as a drug mule who inadvertently acquires superhuman powers.

On October 2013, He signed with C-JeS Entertainment.

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