Park Mi-seon was born in Busan, South Korea. As a child, Park displayed a talent for singing, saying, "When I was young, I used to be so shy that I cried when I was told to sing in front of my dad on the Lunar New Year. My mom ended up sending me to a singing academy, hoping it would help me get over my shyness, but the strange thing is that I couldn't sing in front of my mom but I wasn't nervous at all on stage." In 1990, the fifth grader won the top prize in a children's music contest on KBS.

Park began attending college in the United States in 1998, majoring in journalism at Long Island University. In 2000, she took a leave of absence from school and entered in the regional Miss Seoul beauty pageant, placing third, followed by the Miss Korea pageant.

Park first became known to the Korean public not through her acting roles, but as the girlfriend of popular singer-actor Eric Mun (from K-pop boy band Shinhwa), whom she began dating in 2004. Her relationship with Mun overshadowed her acting career during her early years, with the public commonly identifying her as "Eric's girlfriend". In an interview with The Korea Herald, Park said it took about 10 different roles before the tag of "Eric's girlfriend" vanished from the public's perception of her, adding that the only positive of the tag was that she loved him. The couple broke up in 2007.

In 2005, Park made her acting debut in her native country of South Korea with the SBS TV drama My Girl, for which she received unanimously bad reviews. But Park continued to work, appearing in more dramas and making her film debut in the 2006 quirky comedy-horror-musical The Fox Family; gradually her acting showed marked improvement. At first constantly struggling to memorize her lines, Park has admitted that she became more relaxed in her approach to acting, and is able to "feel" her characters better. She became known for playing women who drove men to their destruction and misfortune: In the gangster film A Love, the lover of Park's character goes to prison after defending her, in the MBC drama La Dolce Vita, she was a gold-digging mistress with a lonely soul, in spy film parody Dachimawa Lee, she was a sexy agent, and in the KBS drama The Slingshot, she sacrifices herself and becomes the enemy's possession in exchange for her boyfriend's freedom. Park smilingly said, "I personally don't like femme fatales. Men should be happy because of women, not unhappy."

In 2009, she joined the variety/reality show Family Outing, which features comedians and entertainers dealing with various aspects of rural life. But Park had to leave after six months due to a recurring injury she sustained while filming a previous project.

In an August 2010 interview with Cosmopolitan, Park said, "These days the thing I most think about is, ‘Have I lived well?’ I’m happy when I film dramas or movies, but in this kind of life you should turn back and take stock of your life at least once, and I think that time has come. I want to love. I want to marry soon and live boisterously."

On November 19, 2011 at the Seoul Hyatt Hotel, Park married Park Sang-hun, an office worker at a small company. She gave birth to their first child, a daughter, on September 24, 2013. Their second child, also a daughter, was born on November 14, 2015. In early 2013, Park was among the celebrities investigated then indicted for illegal use of propofol; Park's agency denied the allegations, saying she took the drug for medical reasons after she injured her back doing action scenes for the films Marine Boy and Dachimawa Lee. During the trial, her Doctor testified that she had been taking the drug to treat avascular necrosis at the head of her femur. In October 2013, the Seoul Central District Court found Park guilty of taking propofol 400-500 times over four-and-a-half years (or 8.2 times a month), and she was sentenced to eight months in prison, suspended for two years.

Park made her comeback to the big screen after a two-year hiatus (her last film had been Marine Boy) in 2012's The Scent. She played a seductive woman who is the sole witness to the deaths of her husband and his mistress, whom the detective suspects is the killer yet is drawn to her mystique. Mesmerized while reading the script for the movie, Park said, "I am really excited that I get to play a character that is cool on the outside but is hurt and sad on the inside."

After giving birth and being indicted for propofol use in 2013, Park returned to television with the 2014 cable drama The Greatest Marriage, in which her character struggles to balance single motherhood and a successful career as an anchorwoman.

In 2015, she made her Hollywood debut in Last Knights, an action film set in medieval times about a band of warriors who seek revenge on a corrupt Emperor. She starred alongside Clive Owen, Morgan Freeman, and Korean veteran actor Ahn Sung-ki. With Japanese Director Kazuaki Kiriya at the helm, filming took place in the Czech Republic.