Lee started baseball because of his childhood friendship with Shin-soo Choo. Lee attended Kyungnam High School in Busan, South Korea. At Kyungnam High School, Lee batted fourth and could throw a mid-90s mph fastball as a pitcher. In 2000, he was selected for the South Korean Junior National Team as a pitcher. The team won the 2000 World Junior Baseball Championship in Edmonton, Alberta, Canada, and Lee led the attack alongside Kim Tae-kyun, Choo Shin-soo (the eventual MVP of this event) and Jeong Keun-woo as a cleanup hitter by racking up 3 home runs. He also finished runner-up behind Joe Mauer of Team USA in batting average (.500).

As a rookie, Lee joined the Lotte Giants as a pitcher in 2001. However, following an injury, he was officially changed to a position player for the second half of the 2001 season.

In the 2006 season, Lee won the league’s Triple Crown with a .336 batting average, 26 home runs, and 88 RBIs. This is the second time a hitter has won the Batting Triple Crown in the Korea Professional Baseball league. He finished second in voting for the 2006 MVP behind the Hanhwa Eagles pitcher Ryu Hyun-jin, also the winner of the Triple Crown for pitchers in 2006.

In 2008, Lee was a member of the South Korea national baseball team that won the gold medal at the 2008 Summer Olympics, while he had an average of .360 (9-for-36), 3 home runs, 10 RBIs, 5 runs, and .760 slugging percentage, playing as the designated hitter.

On August 13, 2010, Lee wrote a new chapter in Korean baseball by hitting a home run in eight straight games in the league. The eighth home run was hit at an away match against the Kia Tigers in Gwangju in the top of the seventh inning when he sent former Major Leaguer Aquilino López’s fifth pitch over the left fence of Moodeung Stadium. This tied the existing record in world professional baseball shared by Ken Griffey Jr. in 1993, Don Mattingly in 1987 and Dale Long in 1956. On August 14, 2010, Lee set a world record by hitting a home run in his ninth straight game when, in the second inning of Giants’ second away match against the Tigers, he blasted a three-run homer off Tigers reliever Kim Hee-girl over the center fence of Moodeung Stadium. It was his 38th home run of the season. With his 83rd run that year, he set a new Korean League record with a run in 16 consecutive games. In the 2010 season, Lee enjoyed one of the most dominant offensive seasons in world professional baseball history, leading the KBO in seven offensive categories (batting average, HRs, RBIs, runs scored, on-base percentage, slugging percentage and hits), which made him a Septuple Crown winner (7관왕).

In December 2011, Lee signed a two-year contract worth 760 million yen ($9.78 million) with the Orix Buffaloes of the Nippon Professional Baseball. During his 4 years in the NPB (2012~2015), he recorded the highest OPS rate during this time.

On July 20, 2012, at the Osaka Dome, Lee won the NPB Home-run Derby against Wladimir Balentien of the Tokyo Yakult Swallows. He belted 6 home runs while Balentien made no home runs. He was rewarded with 500,000 yen ($6,400). He ended his season with a .286 average, 24 home runs, and 91 RBI.

On February 3, 2016, Lee signed a minor league contract with the Seattle Mariners of Major League Baseball. The Mariners added Lee to the 40-man roster on March 27, 2016.

On April 8, 2016, Lee recorded his first career major league hit, a home run off of Eric Surkamp in a game against the Oakland Athletics. On April 13, 2016, Lee hit a pinch hit walk off home run to beat the Texas Rangers. This was the first rookie pinch hit walk off in Mariners history. On May 4, 2016, Lee hit two home runs in a 9–8 victory over the Oakland Athletics.

On June 10, 2016, Lee recorded back-to-back home runs off of Derek Holland, totaling 4 RBI to propel the Mariners to a 7–5 victory over the Texas Rangers.

On January 24, 2017, Lee signed a four-year, $12.9 million contract with the Lotte Giants. The contract was the largest for a free agent in KBO history. Lee’s 2017 season was a success, as he hit .320 with 34 home runs and 111 RBIs. He was instrumental in helping Lotte return to the postseason for the first time in five years.

In 2018, he hit .333 with 37 home runs and 125 RBIs. However, in 2019, Lee failed to reach 20 home runs for the first time in 10 years, and was sent to the second division due to injuries.