It was a double blow for the 28-year-old from Cairo on the day his ten-month reign as world number one officially came to an end - and further celebration for the Englishman who rose to six in the new world rankings.
On paper, the last sixteen clash in the premier event on the PSA World Tour was an upset - but Willstrop had not lost to the Egyptian since November 2006, and went into the match 8-6 up on a career head-to-head count.
There was further confusion before the match - the first of the evening at the spectacular seaside setting - when forecast rain and thunder threatened to move the session back to the conventional indoor Salmiya Club courts.
Darwish led in all four games, but Willstrop maintained his focus to take the first two before the new world number three battled back to reduce the deficit.
Again the favourite took leads in the fourth game - going up 5-2, 8-6 and 9-8 - but again the tall Yorkshireman refused to be overawed. The 26-year-old from Leeds ultimately claimed his 11-7, 11-7, 3-11, 11-9 victory after 58 minutes - and a place in the last eight for the fifth time in six years.
"He was quite dominant in the third and fourth games and put me under a lot of pressure," said Willstrop. "He didn't give me a lot of chances - he's one of the best players in the world at getting the ball into the back corners."
Willstrop shrugged off suggestions that the hour delay in the start of the match - and the uncertainty about whether it would be played on the indoor court or on the glass court - affected him: "I think I coped with it pretty well - though I'm not sure other sportsmen would have done so. The issue was dealt with as well as it could be by all concerned."
Out of action for three months following ankle surgery in April, Willstrop now feels he is fully recovered: "It was an unbelievable experience - I'd never had an operation before.
"I almost lost the first match I played afterwards, at the World Games in Taiwan, then managed to get to the final. Looking back, that was a vital experience. I then got to the semis of the US Open and the final of the British Open - which was fantastic.
"I think I'm now back to where I was if I can beat the best player in the world," concluded Willstrop.
The second match was also an Anglo-Egyptian clash - in which three-time former champion Amr Shabana, the fourth seed, avenged his country's defeat in the opening match by beating Englishman Daryl Selby, seeded 22, 11-9, 11-6, 11-8 in 48 minutes.
Selby was not only celebrating his 27th birthday but his first appearance in the world's top 20 at a career-best ranking of 17. But only 24 hours earlier, the Essex player had upset higher-ranked Malaysian Mohd Azlan Iskandar - surviving a 135-minute marathon!
"I played well - the best I possibly could," said Selby after his second successive third round match in the World Open. "I could have done with that first game, but he played two good rallies from nine-all.
"It was such a huge game for me. But I thoroughly enjoyed it - the crowd were very appreciative, for both sides, and it's a brilliant arena for squash.
"I believed I had a chance to win - but he was just too good," concluded the birthday boy.
There was further English success when both Nick Matthew and Peter Barker made the last eight. Fifth seed Matthewmaintained his unbeaten game record in the event earlier at the Salmiya Club with a clinical third round displayagainst Cameron Pilley, the last remaining Australian in the championship.
On the day that he was confirmed as the new world number four - his career-best ranking - Matthew crushed the tall 20th seed from New South Wales 11-6, 11-3, 11-2 in just 35 minutes.
The 29-year-old from Sheffield has enjoyed a topsy-turvy ride with the Australian - beating him on the way to winning his second British Open title in September, then losing later in the month in Cairo in a 90-minute four-game marathon.
"You're always pleased when you beat someone - especially when he beat you the last time," said a delighted Matthew after his swift win.
"I've been slightly fortunate with the draw - playing two people who have survived tough five-game wins the match before.
"Cam is a confident player - so I was determined to get a good start. But, as my coach David reminded me between games, when you've got the lead, you've got to keep pushing - so I kept attacking him."
After three rounds at the Salmiya Club, Matthew will now move into the new environment of the all-glass court at Green Island. "I'm looking at this as two separate tournaments - three matches here and hopefully another three on the glass court.
"I've got the first tournament out of the way, so now I can look forward to the next," explained the new world number four.
It was a relieved Englishman Peter Barker that ended Egyptian outsider Hisham Mohd Ashour's run to claim his first appearance in the quarter-finals.
Hisham, the 21st seed and older brother of the reigning champion Ramy Ashour, earned his surprise place in the last sixteen after upsetting 10th seed Adrian Grant, also from England, in the previous round.
Barker was in control for the first two games - but the 27-year-old from Cairo battled back to take the third game and led in a closely-contested fourth.
But the seventh seed from London maintained his composure and after 57 minutes secured his 11-6, 11-5, 8-11, 11-9 victory - and a place in the last eight for the first time at his fifth attempt.
"I feel relieved most of all - happy, yes, but more relieved," explained the left-hander afterwards. "Somehow, I just couldn't relax - I played well in the first two games but then let him get back in the third.
"But it's great to be in the quarter-finals of the worlds for the first time - after all, that's where it all happens.
"There are eight players remaining so one of us has got to win it - so let's hope it's me!
"The pressure's off, but I'm not going to relax. I played my best squash in the first two games so I hope I can replicate that tomorrow," added the world number nine.
Egypt will also boast three players in the quarter-finals as former champion Amr Shabana will be joined by title-holder Ramy Ashour and ninth seed Wael El Hindi.
The experienced Wael El Hindi, making his eight appearance in the event, faced 21-year-old compatriot Tarek Momen, the 25th seed who pulled off the shock of the tournament by ousting Australian David Palmer, a two-time former champion, in the previous round.
The underdog took the first game - but 29-year-old El Hindi fought back to win 10-12, 11-6, 11-7, 11-6 in 61 minutes to earn his first quarter-final appearance since 2006.
Ramy Ashour, the third seed, recovered from a mid-match crisis to beat Dutchman Laurens Jan Anjema. The 14th seed from The Hague was looking to reach the quarter-finals for the first time and got on top of his higher-ranked opponent to draw level after the second game.
But the 22-year-old from Cairo, who kept urging himself to calm down during the match, reclaimed control of the encounter to close out an 11-5, 7-11, 11-5, 11-7 victory.
Eighth seed Thierry Lincou became the first Frenchman to reserve a place in the quarters. The World Open champion in 2004 survived a hard-fought 53-minute clash with Alister Walker, beating the 15th seed in four games.
Walker dropped the first game, but failed to convert 6-1 and 7-4 leads in the second. However, the underdog Englishman grabbed the third and fought back from 1-6 down to draw level in the fourth.
But the experienced Frenchman lifted his game to clinch an impressive 11-2, 11-8, 4-11, 11-6 win - to earn his seventh quarter-final in ten appearances since 1998.
"I had a bit of a loss of concentration, especially in the third - I didn't push mentally to keep the pace up," explained the former world number one from Marseille. "And when you let the pace go, he's dangerous player.
"I've heard him referred to as the English Egyptian - and it's true, he plays like an Egyptian. Ali beat Shabana a few weeks ago - he's capable of beating anyone."
Lincou was joined by compatriot Gregory Gaultier after the last match of the night at Green Island. The new world number one from Aix-en-Provence was in commanding form as he despatched Malaysian Ong Beng Hee, the 13th seed, 11-4, 11-5, 11-9 in 42 minutes.
 James Willstrop (ENG) bt  Karim Darwish (EGY) 11-7, 11-7, 3-11, 11-9 (58m)
 Thierry Lincou (FRA) bt  Alister Walker (ENG) 11-2, 11-8, 4-11, 11-6 (53m)
 Amr Shabana (EGY) bt  Daryl Selby (ENG) 11-9, 11-6, 11-8 (48m)
 Wael El Hindi (EGY) bt  Tarek Momen (EGY) 10-12, 11-6, 11-7, 11-6 (61m)
 Peter Barker (ENG) bt  Hisham Mohd Ashour (EGY) 11-6, 11-5, 8-11, 11-9 (57m)
 Ramy Ashour (EGY) bt  Laurens Jan Anjema (NED) 11-5, 7-11, 11-5, 11-7 (48m)
 Nick Matthew (ENG) bt  Cameron Pilley (AUS) 11-6, 11-3, 11-2 (35m)
 Gregory Gaultier (FRA) bt  Ong Beng Hee (MAS) 11-4, 11-5, 11-9 (42m)
 James Willstrop (ENG) v  Thierry Lincou (FRA)
 Amr Shabana (EGY) v  Wael El Hindi (EGY)
 Ramy Ashour (EGY) v  Peter Barker (ENG)
 Gregory Gaultier (FRA) v  Nick Matthew (ENG)
Issued by iSPORTmedia