Landon is the son of Canadian Tim Donovan and Donna Kenney Cash. Donovan grew up in Redlands, California, and attended Redlands High School before transferring to Redlands East Valley. Landon signed a professional contract with Bayer Leverkusen in February 1999 at the age of 17, shortly before playing in the U-17 World Championship, where he won the Golden Ball as the tournament's best player.

Donovan could not break into the first team with Leverkusen, however, and, unhappy with his situation in Germany, was loaned to the San Jose Earthquakes of Major League Soccer for the beginning of the 2001 season. In MLS, Donovan had immediate success, leading the Earthquakes to MLS Championships in 2001 and 2003 and becoming one of the most recognizable faces of soccer in America. In four years in the league, he scored 32 goals and 29 assists in league play, and ten goals and six assists in the playoffs. Donovan was named U.S. Soccer Athlete of the Year in 2003.

Donovan has also been successful on the international stage. After starring in the 2000 Summer Olympics, he earned his first cap for the U.S. National Team on October 25, 2000 against Mexico. He was integral to the United States' run to the quarterfinals of the 2002 World Cup in Japan/South Korea, scoring two goals. As of end of 2005, he has amassed 73 caps for the US, scoring 25 goals, including a rare four-goal game against Cuba in 2003. On April 11, 2006, Donovan became the United States' all-time assist leader with 23 when he set up Ben Olsen. Donovan passed Cobi Jones.

On June 3, 2004, Bayer Leverkusen announced that Donovan would return to the club in 2005, and Landon followed suit, announcing his return to Germany on November 23, 2004. He then became the first man to be named U.S. Soccer Athlete of the Year two years in a row, taking the award for that year.

In early 2005, after failing to perform in his limited chances with Bayer, Donovan stated his intentions to come back to MLS. His wish was quickly granted, but it was not San Jose that he returned to. Los Angeles traded leading scorer Carlos Ruiz to F.C. Dallas to get on top of the allocation pecking order and signed Donovan on March 31, 2005. In his first season with the Galaxy, Donovan scored 12 league goals and 10 assists and added four goals and an assist in the playoffs as the Galaxy won the MLS Cup (his third MLS championship to date), making him MLS' all-time leading scorer in the playoffs with 14. He was named to the MLS All-Time Best XI after the season.