Even though the Argentine is playing at Paris for the first time in five years, Murray would do well not to consider himself the favourite given how he was beaten in five sets by Del Potro in last year's Davis Cup semi-finals.
Raising his level, del Potro slid a slice backhand to save the first and denied the second on a Murray backhand error.
Whenever and wherever these two meet, rallies can erupt like fireworks and today's 10th encounter-their first clay-court clash in eight years-did not disappoint. I have been out for a long time.
"It was tough, because I think [Del Potro] was playing much better than me in the first set. Whoever won that first set would have the momemtum as it would have been very hard to come back in these heavy, slow conditions", said Murray. Whoever had won that first set had big momentum.
"Too much frustration. I couldn't believe that I lost that set, because I had many opportunities to win".
Zheng, in partnership with Romanian Irina-Camelia Begu, had to come back from one set down to beat Abigail Spears and Katarina Srebotnik 1-6, 6-4, 6-3.
He called for umpire Carlos Bernardes to check and stood for a good minute leaning on the net with head in hands after Bernardes admitted he could not see the mark and stuck with the line judge's call.
While Khachanov is through to the last 16 at a slam for the first time, it is seven years and 25 tournaments since Murray failed to at least make the fourth round.More news: Apple CEO Tim Cook to address 2017 graduates at MIT
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Andy Murray can start to look ahead at the French Open after defusing the power game of Juan Martin del Potro to reach the fourth round. From painful defeats del Potro has not managed to move on the Argentine gradually wilted, and Murray each game added and won a legitimate victory.
A remarkable effort saw Del Potro break back for 5-5, before he dropped serve and allowed his opponent to control proceedings and take the set 7-5 with his fourth ace of the day. The third arrive at 7-6 in the tiebreaker - the excruciating double-fault. "I would give a little bit of the favoritism to her, but at the same time I feel like I have been playing well".
Pliskova was the runner-up at last year's U.S. Open.
Cilic, the 2014 U.S. Open champion, will next face South African Kevin Anderson, who beat Britain's Kyle Edmund 6-7 (6), 7-6 (4), 5-7, 6-1, 6-4.
Croatia's Marin Cilic clenches his fist as he plays Spain's Feliciano Lopez during their third round match of the French Open tennis tournament at the Roland Garros stadium, Saturday, June 3, 2017 in Paris.
The third-seeded Wawrinka, the French Open champion in 2015, will face 15th-seeded Gael Monfils.
The unseeded Cornet was a surprisingly easy victor over No. 9 Agnieszka Radwanska of Poland, 6-2, 6-1, while No. 28 Garcia edged Hsieh Su-wei of Taiwan 6-4, 4-6, 9-7.