Ji-Sung, who won his 100th cap in last Tuesday's Asian Cup semi-final defeat by Japan, said chronic knee injuries had forced him to make the decision.
However, the 29-year-old expects to continue playing for United for up to four more years.
"It was a great honour to play for the national football team," said Park. "If there were no injuries, I could have continued, however, I have no choice."
Park, who was not included in South Korea's team for the 3-2 win over Uzbekistan in the third-place match in Qatar, added: "Above all, I would like to make way for team-mates who have been making remarkable progress."
He became the first South Korean to play in a Champions League final when Manchester United lost to Barcelona in 2009.
Park, who joined United from PSV Eindhoven in 2005, has also won three Premier League titles and three League Cups with the English club.
He made his international debut in 2000 and he was part of the team which reached the World Cup semi-finals in 2002, the best performance by an Asian team in the competition.
Park also played in the 2006 and 2010 tournaments.
Former Tottenham defender Lee Young-pyo, 33, has also quit international football.
Both Park and Lee were thrown into the air in celebration by their fellow South Korean players, after the third-place finish ensured automatic qualification for the 2015 Asian Cup.
Kwang-rae said: "Park Ji-sung and Lee Young-pyo have done a remarkable job for the prosperity of Korean football.
"It would be better if I could retain both of them in the national team but other players have done an excellent job."
Midfielder Ki Sung-yeung added: "They have been really great players for 10 years and I am really proud of them and they showed to the people all over the world that Korean football is getting better."
Source: BBC Sport
Source: BBC Sport