quality:corruption, information:highlighting, stylistic:style_transfer, structural:expansion, stylistic:tone
2006: Second French Open title

Nadal missed the Australian Open because of a foot injury. In February, he lost in the semi-finals of the first tournament he played, the Open 13 tournament in Marseille. Two weeks later, he handed Roger Federer his first loss of the year in the final of the Dubai Open (in 2006, Nadal and Andy Murray were the only two men who defeated Federer), thus ending Federer's 56-match winning streak on hard courts. Nadal was then upset in both the semi-finals of the Indian Wells Open by James Blake, and in the second round of the Miami Masters by Carlos Moyá, who thus ended Nadal's 22-match win streak over fellow Spaniard players.

On European clay, Nadal won all four tournaments he entered and 24 consecutive matches. He defeated Federer in the final of the Monte Carlo Masters in four sets. The following week, he defeated Tommy Robredo in the final of the Torneo Godó tournament in Barcelona. After a one-week break, Nadal won Italian Open title defeating Federer in a fifth-set tiebreaker in the final, after saving two match points and equaling Björn Borg 's tally of 16 ATP titles won as a teenager. At five hours and five minutes, this is the longest match Federer and Nadal have ever contested and it is considered to be where the Federer–Nadal rivalry began in earnest, with The New York Times comparing it to the Muhammad Ali – Joe Frazier rivalry in boxing on the following day. Nadal then broke Argentinian Guillermo Vilas 's 29-year male record of 53 consecutive clay-court match victories by beating Robin Söderling in the first round of the French Open. Vilas presented Nadal with a trophy, but commented later that Nadal's feat was less impressive than his own because Nadal's winning streak covered two years and was accomplished by adding easy tournaments to his schedule. Nadal went on to face Novak Djokovic in the quarterfinals, the first-ever meeting of their historic rivalry, which Nadal won via a retirement from Djokovic after Nadal took the first two sets. He then beat Ivan Ljubičić to set up a final against Federer. The first two sets of the match were hardly competitive, as the rivals traded 6–1 sets. Nadal won the third set easily and won the fourth in a tiebreaker to become the first player to defeat Federer in a Grand Slam tournament final.

Nadal injured his shoulder during a quarterfinal match against Lleyton Hewitt at the Artois Championships, played on grass at the Queen's Club in London. Nadal was unable to complete the match, which ended his 26-match winning streak. Nadal was seeded second at Wimbledon, and was two points from defeat against American qualifier Robert Kendrick in the second round before coming back to win in five sets. In the third round, Nadal defeated No. 20 Andre Agassi in straight sets in Agassi's last career match at Wimbledon. Nadal also won his next three matches in straight sets, which set up his first Wimbledon final, which was against Federer, who had won this tournament the three previous years. Nadal was the first Spanish man since Manuel Santana in 1966, to reach the Wimbledon final, but Federer won the match in four sets to win his fourth consecutive Wimbledon title.

During the lead up to the US Open, Nadal played the two Masters tournaments in North America. He was upset in the third round of the Rogers Cup in Toronto and in the quarterfinals of the Cincinnati Open by Juan Carlos Ferrero. Nadal was seeded second at the US Open, but lost in the quarterfinals to No. 54 Mikhail Youzhny in four sets.

Nadal played only three tournaments for the remainder of the year. Joachim Johansson, ranked No. 690, upset Nadal in the second round of the Stockholm Open. The following week, Nadal lost to Tomáš Berdych in the quarterfinals of the Madrid Masters. During the round-robin stage of the year-ending Tennis Masters Cup, Nadal lost to James Blake but defeated Nikolay Davydenko and Robredo. Because of those two victories, Nadal qualified for the semi-finals, where he lost to Federer. This was Nadal's third loss in nine career matches with Federer.

Nadal went on to become the first player since Andre Agassi in 1994–95 to finish the year ranked No. 2 in consecutive years.