Roger Federer is the only player who can stop Nadal sealing the year-end honour for a fourth time.
Del Potro's wrist problems have been well documented down the years and at 2-2 in the deciding set he fell awkwardly on to his non-playing hand, dropping on to it with most of his weight.
Del Potro received lengthy treatment to the area - which has undergone surgery in the past - before battling through 4-6 6-1 6-4.
Federer made another matchup by beating Richard Gasquet 7-5, 6-4.
"I saw his frustration, for sure", del Potro said.
"I don't understand how I can lose a match where I get broken one time in three sets and not managed to get any chances on his serve", said Zverev, who is tipped to one day make world number one.
"But if nothing risky happened, I will be here to play tomorrow and doing my best".
Wimbledon runner-up Marin Cilic also eased into the quarter-finals with a 7-6 (7-1) 6-4 defeat of American Steve Johnson.
In the quarterfinals, Nadal will play sixth-seeded Grigor Dimitrov of Bulgaria, who got past Sam Querrey of the US 6-3, 7-6 (3).
Cilic will face Spain's Albert Ramos-Vinolas, who beat German Jan-Lennard Struff 7-6 (4), 6-4.
The shot, came early in the match - only the third game - and wouldn't have any bearing on the set either, with Nadal taking it 6-4.
He stormed back to take the second on a tie-break and Croft says it was down to a change of approach in the Bulgarian's game - and he mentally got the better of the Spaniard.
On-fire Nadal took the first set of their last-eight clash this morning before Dimitrov hit back.
In the third set, Nadal saved the one break point he faced in the match in the fifth game, and broke serve in the sixth to set up victory.
A relieved Nadal looked up to the heavens and raised his arms at the end.