After graduating Bupyeong High School, Lee joined his hometown club, Incheon United in 2004. However, he was surplus to requirement, and usually stayed in the reserve squad. In 2006 season, he was nominated as the Best Player in the R League, the Korean reserves league for Incheon Reserves. Then, Daegu FC’s manager Byun Byung-joo signed him at the beginning of 2007 season.

Lee was selected for the 2005 FIFA World Youth Championship in Netherlands. However, for most matches, he remained in the bench, not playing a single match in the group stage, while his team-mate Park Chu-young made good impressions. He was confirmed in the Summer Olympics squad in 2006, and became the most valuable player in the squad to qualify for the Olympic games. He was selected for the 2007 AFC Asian Cup, and also capped for the South Korea under-23 team in qualification for the 2008 Summer Olympics.

On 29 June 2007, Lee made his senior team debut in a friendly against Iraq through substitution in the second half. Lee also managed to score his debut goal from an assist made by Lee Chun-Soo. On 15 October 2008, Lee scored two goals in a qualification match of the 2010 FIFA World Cup against United Arab Emirates. On 19 November 2008, Lee scored the most important goal in his international career yet in an away game against Saudi Arabia, which ended South Korea’s nineteen-year losing spell against the Saudis. Although he played in most of the qualification campaign, he was not named for the team to participate in the 2010 World Cup.

Newly appointed manager Byun brought intensively aggressive football to Daegu, named the “Bullet Football”, and Lee began to claim the spotlight with his powerful dribbles. In his first season, he came seventh in the top scorers chart with eight goals, then came fifth in the 2008 season with eleven goals. In both seasons, he became top scoring South Korean of the league between foreign players. In his last game for Daegu, against Pohang Steelers in the semi-final of Korean FA Cup, he played full-time even with injury, but failed to rescue his side from a defeat. Daegu wanted to keep Lee, but he was willing to move to Europe, so in December 2008, his contract with Daegu expired, meaning he became a free agent. Several European clubs showed their interest in acquiring his talents. He was offered a trial at English Premier League club Blackburn Rovers, however he turned them down because he worried about the competition for a starting position in the club. In February 2009, it was again rumoured that Blackburn would be interested in signing the still free agent Lee Keun-ho, but again, he rejected the opportunity.

In April 2009, he signed for Júbilo Iwata, on a nine months contract. He made six goals and four assists in his first eight league games. In June, he left the club, with some media linking him with Paris Saint-Germain in the French Ligue 1; however, the move did not materialize. In June 2010, he signed for Gamba Osaka, and spent his best season in the 2011 J1 League, having scored 15 goals for Gamba Osaka at 32 matches.

On 10 January 2012, he returned to K League 1, signing for Ulsan Hyundai on a three-year deal. In his first season with the club, he won the 2012 AFC Champions League that was named as the Most Valuable Player of the tournament and also named as the Asian Footballer of the Year at the end of the year. He was transferred on 1 January 2013 to Sangju Sangmu on loan to complete his military service as per South Korean law.

Lee was included in South Korea’s squad for the 2014 FIFA World Cup by showing good performances with three goals in the final round of the qualification. In their first group stage match against Russia on 17 June 2014, he came on as a substitute for Park Chu-young in the 52nd minute and scored his first ever World Cup goal in a 1–1 draw when his shot from outside the box was spilled by goalkeeper Igor Akinfeev over his head and over the line. He also assisted Koo Ja-cheol’s goal in the second match against Algeria.