The 18-year-old needed a close tie-break as he defeated the world number two 3-6, 6-4, 7-6 to advance to the last eight. The Canadian, who was handed a wildcard for the tournament, has produced some impressive results to make the third round and set up his first meeting against a top-10 player. Seventh-seeded Bulgarian Grigor Dimitov topped Mischa Zverev 6-3, 3-6, 6-3.
Shapovalov, 18, was the youngest player since Nadal in 2004 to reach the round of 16 in a Masters Series tournament.
Nadal's defeat means Andy Murray hangs on to his world number one ranking for one more week until the Cincinnati Masters, where Nadal or Roger Federer will overtake him. With the set being brought to a tiebreak, del Potro had the upper hand when he jumped out to a 3-1 lead, looking on course to send the match into a deciding set. "That was important. I take it how it is and hope that this match gives me some better rhythm and confidence". He arose blowing kisses to the crowd.
"His ball is just so heavy and he's such a warrior out there".
What it showed was that Zverev knows how to win even when the pressure is on and his game isn't quite there. Dancing around his backhand, Nadal roped a forehand victor wrapping up the 38-minute opening set. The 29-year-old double faulted twice in his first service game and had difficulty handling Federer's pinpoint serves.
The younger lefty confronted a love-30 hole with a shot-making tear. Shapovalov recorded two of his nine aces in the tiebreaker.
The thick thatch of blond hair was flying as Shapovalov launched himself into a forehand that stuck on the baseline for set point. His serve is already excellent, and whilst his groundstrokes can wilt when he gets nervous, as seen by his failed attempt to serve out the match against Del Potro, that will surely improve with age.
A pulsating 10-deuce game spanned almost 15 minutes.
Shapovalov revealed he grew up watching Nadal.
Federer, a big endorser of #NextGenATP talent, came away impressed with Shapovalov after watching the Canadian teenager play in the Wimbledon juniors a few years back.
That unrattled Shapovalov, but only momentarily after breaking Nadal fortuitously to force a third and deciding set.
A gritty hold edged the Canadian ahead, 3-2.