The Swiss played some of his best tennis this year but it was still not enough to stop him from being on the receiving end of a 7-6 (3), 2-6, 6-4 defeat against the powerful Argentine and his 220 kph serve.
Top seed Roger Federer suffered a shock 6-3, 6-4 defeat to Germany's Daniel Brands in his opening match at his home Swiss Open on Thursday - the latest setback for the former world number one.
The Swiss champion was at his breath-taking best as he crafted 48 exquisite winners during a 90-minute match that seemed more an exhibition of his shot-making than a charge towards a record ninth Wimbledon title.
American Sam Querry became the latest Wimbledon giant slayer on Saturday as he beat defending champion Novak Djokovic 7-6(6) 6-1 3-6 7-6(5) in the third round. The defeat ended Djokovic's run of winning 30 consecutive grand slam matches. The world number one had arrived at the All England Club as the reigning champion at all four grand slam tournaments.
Andy Murray and Rafael Nadal were winners but six seeds were beaten in a day of upsets in the second round at the Rogers Cup in Montreal on Thursday.
Rafael Nadal is confident he will be ready to compete in this week's Miami Open despite turning his ankle in practice, the second seeded Spaniard said on Tuesday.
Roger Federer is looking for a change of fortune. And in that direction, the former World No 1 split from his American coach Paul Annacone on Saturday.
The year's final grand slam began with an upset as 13th-seeded Frenchman Richard Gasquet was upended 6-2 6-2 6-3 by Britain's world number 84 Kyle Edmund at the U.S. Open on Monday. Gasquet, who has reached the last 16 at Flushing Meadows four times in his career, was outplayed throughout and his U.S. Open experience lasted just one hour, 41 minutes.
Roger Federer's struggles in 2013 are unlikely to hasten his exit from the game and the Swiss master could hit back and win next year's Australian Open, according to tennis great Rod Laver.
Klitschko and his brother Vitali, also a former world heavyweight champion and now the mayor of Kyiv, have both taken up arms against invading Russian forces.
Second seed Angelique Kerber stayed on track in her quest to unseat Serena Williams as world number one by beating Mirjana Lucic-Baroni of Croatia 6-2, 7-6(7) on Wednesday to reach the third round of the US Open.
Juan Martin del Potro continued his encouraging buildup to the Australian Open by reaching the semi-finals of the Sydney International on Thursday, but women's contender Petra Kvitova was stunned by a Bulgarian qualifier in the last four.
World number five Juan Martin del Potro began his 2014 season with a win, albeit a scrappy one over Frenchman Nicolas Mahut to advance to the quarter-finals of the Sydney International on Wednesday.
Dustin Brown's audacious attempt to unseat defending Wimbledon champion Andy Murray with a show-boating brand of serve and volley tennis was always likely to end in failure.
Former US Open champion Juan Martin Del Potro underlined his status as a dark horse for next week's Australian Open by hammering Dmitry Tursunov to reach the final of the Sydney International on Friday.
Croatian Cilic, who lost last year's final to Roger Federer, underlined his credentials for another Grand Slam title bid to add to his U.S. Open triumph in 2014.
Serena Williams and Marin Cilic both survived third round scares on Friday to keep their US Open title defences on track but there was no escape for Rafael Nadal with the twice-winner going down in a late night thriller.
Summary of sports events and persons who made news on Saturday
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