I am looking forward to managing this great team with so many great riders who can hopefully do better than me one day and win the tour de france and the vuelta were i came 2nd behind team mate alberto contador.

Leipheimer was born and raised in Butte, Montana, where his parents ran a sporting-goods store. As a youth, his main sport was skiing, but he became interested in cycling and a skiing accident led to him directing his career hopes towards cycling. He moved to Belgium after graduation to race as an amateur, and turned professional in 1997. In 1995 Leipheimer won the Tour of Namur as an intern for the British F.S. Maestro – Frigas team.

Leipheimer, riding for Team Einstein, won the 1996 U.S. National Criterium Championships in Grandview Heights, Ohio, but tested positive for ephedrine, a banned substance. He eventually forfeited his title, prize money and national champion's jersey. Leipheimer's family later claimed that the positive test was not indicative of doping, but rather, the result of his taking allergy medicine Claritin-D to relieve hay fever. Leipheimer turned professional in 1997 with the Colorado Cyclist team. In 1998, he changed teams and was hired by Team Saturn, with which he won the U.S. National Time Trial Championship in 1999.

Leipheimer joined the US Postal team in 2000. His breakthrough came in the 2001 Vuelta a España, his first Grand Tour, in which he was riding in support of team leader Roberto Heras. Going into the final stage, an individual time trial in Madrid, Leipheimer was fifth, trailing his leader, who was third, by about a minute. During that time trial, Leipheimer moved ahead of two riders, including Heras, in the general classification to finish third overall, the first American to reach the podium in the Vuelta. He joined Dutch team Rabobank in 2002, and he finished eighth in his first Tour de France. Leipheimer represented the United States in the 2004 Athens Olympics road race, but did not finish. He finished ninth in the Tour de France of that year.

Riding for the German team Gerolsteiner, Leipheimer finished 6th in the 2005 Tour de France. On August 23, 2005, Leipheimer won the Deutschland Tour by 31 seconds, ahead of T-Mobile Team's Jan Ullrich and Gerolsteiner teammate Georg Totschnig. He had solidified his lead by defeating Ullrich in stage four on the Rettenbachferner, the highest climb in European racing that year at 2,670m.
In August 2010, Leipheimer was accused of having suspect blood values during the 2005 Tour de France by Hans-Michael Holczer, his former team manager at Gerolsteiner, in his book Garantiert Positiv (Guaranteed Positive, in English). According to Holczer, Leipheimer showed blood values that indicated a "high probability of blood manipulation" and were so suspicious that one UCI official suggested that he should be withdrawn from the race. Holczer said that he refused to withdraw Leipheimer because the team was "facing total bankruptcy" due to the sponsor's nervousness about the team's involvement in other doping scandals. In February 2006, Leipheimer was a favorite to win the inaugural Tour of California. He took the leader's golden jersey on the first day by winning the prologue to San Francisco's Coit Tower, but eventually finished sixth behind Floyd Landis and won the competition for best climber. Leipheimer won the 2006 Dauphiné Libéré, having gained the overall lead on the stage to Mont Ventoux. He was considered a contender in the 2006 Tour de France after several favorites, including Ivan Basso and Jan Ullrich, were suspended because of the Operación Puerto doping case: Leipheimer, who had been sixth the previous year, was the highest-placed rider returning. However, his final position was 12th, 18 and a half minutes behind winner Floyd Landis.

Leipheimer re-signed with Tailwind Sports Corp. and Capital Sports & Entertainment, managing companies for the U.S. Postal and, later, the Discovery Channel cycling teams. Leipheimer was team leader in the 2007 Tour of California, which he won after leading the race from start to finish. In the Paris-Nice race, he supported teammate Alberto Contador, who won. He placed third in the 2007 Tour de France, 31 seconds behind the winner, Contador, although he was retroactively stripped of this third place finish when he confessed to doping in 2012. Leipheimer also won stage 19, the last individual time trial. Discovery Channel disbanded at the end of the season. Leipheimer won the 2007 USA road championship, 1m 11s ahead of Discovery teammate and defending champion George Hincapie.

Leipheimer joined Astana, managed by Johan Bruyneel, former manager of U.S. Postal and Discovery Channel. Astana was banned from the 2008 Tour de France because of doping scandals in the 2007 Tour, although all involved in those scandals had been replaced. Leipheimer created a website to petition, unsuccessfully, for admittance to the 2008 Tour. Leipheimer won the 2008 Tour of California. At the last minute, Astana was admitted to the Giro di Italia, and Leipheimer finished 18th, helping teammate Contador to victory. He won the bronze medal at the 2008 Beijing Olympic Games in the road time trial. Leipheimer won both time trials of the 2008 Vuelta a España, leading the race after the first stage, and placing second overall behind Contador.
Leipheimer began 2009 by winning the Tour of California for the third consecutive year. He broke away during the final climb of stage 2 and led after the stage. Leipheimer won stage 6, the Solvang individual time trial. Astana teammate Lance Armstrong, in his second race after returning from retirement, rode for Leipheimer. Leipheimer won the 2009 SRAM Tour of the Gila with Astana teammates Chris Horner and Armstrong, who finished second but, as UCI regulations meant that Astana were ineligible for the event, the three rode as Team Mellow Johnny's, named after Armstrong's bike shop. In May, Leipheimer rode for Astana in the Giro d'Italia and finished sixth overall, the team's best placement. Later, the second place finisher Danilo Di Luca tested positive for a banned substance and was stripped of his title, moving Leipheimer up to a fifth place finish in the records. Riding with Astana in the 2009 Tour de France, Leipheimer broke a wrist in a crash near the end of stage 12, when he was fourth overall, and abandoned the race.

Leipheimer moved, along with Armstrong and several others from Astana's 2009 team, to Team RadioShack for 2010. He won his second consecutive SRAM Tour of the Gila in April. At the 2010 Tour de California Leipheimer finished in third place overall. Leipheimer was favored to lead the team in California again for 2011, but became the team's chief domestique instead, riding in support of Chris Horner's eventual victory, after the latter posted a stronger time on mountainous stage four into San Jose. Leipheimer also won the stage finishing at the Mount Baldy ski area, and was second in the individual time trial. In his next race, the Tour of Switzerland, Leipheimer overhauled the race leader Damiano Cunego by 4 seconds in the final time trial stage. Leipheimer won the first edition of the USA Pro Cycling Challenge, winning the first stage and coming second in the third stage time trial.

Leipheimer joined Patrick Lefevere's Omega Pharma-Quick Step team for what was supposed to be the 2012 and 2013 seasons. He started his year by winning the Tour de San Luis in Argentina. However, while on a training ride on the eve of the Vuelta Ciclista al Pais Vasco, he broke his fibula when he collided with a car. He stated that he thought he would die when the accident happened. He returned to competition at the Tour of California, where he won the "Most Courageous" jersey after stage one, in recognition of his return from the serious injury. He finished the race in sixth overall.
Leipheimer followed his California performance with third place overall in the Tour de Suisse. Leipheimer won a stage of the Tour of Utah, and finished third overall in the USA Pro Cycling Challenge, having led the race for one day. Omega Pharma-Quick Step abruptly terminated Leipheimer's contract in October, one week after he admitted to having doped for eight years.