The Holland international will sit out the remainder of the campaign after damaging an anterior cruciate ligament in his country's Euro 2016 qualifier in Kazakhstan on Saturday with Rob Elliot ready to stand in for him.
McClaren said: "It's a massive blow for us, you're talking about one of the best players in our team. He's a vital player, very important, and he'd get us 18 or 20 points a season with the way he plays.
"To lose that is devastating. We've had a couple of days to get over it, but for him, the shock of starting to get injured is starting to appear. In the last day or two, he's been a little bit down, but that's football and he'll recover.
"He'll get the best treatment and a good operation, and we wish him well with that. In the meantime, it's time for Rob Elliot to step forward and fill his boots. He needs to step up and perform."
Krul's loss could hardly have come at a worse time with Newcastle sitting at the foot of the Premier League table without a win to their name and only three points to show from their opening eight fixtures.
McClaren could be forgiven for bemoaning his luck too after speaking to his keeper earlier in the day and being told he would be on the bench against the Kazakhs, only to then be asked to step in in place of Jasper Cillessen.
The Magpies' head coach said: "When that happened, people who have worked here for many years were saying, 'For some reason, it's always Newcastle'. Here, it just seems to be one disaster after another.
"But you have to get on with it. This is football, and this is what happens.
"I couldn't believe the text I got on Saturday evening. It was incredible because I'd just spoken to Tim earlier in the day to wish him luck, and he'd said he was on the bench and wouldn't be playing. I said, 'Well, at least you'll be fit for next week'.
"So to get that text didn't exactly make my night."
MAN CITY 6 NEWCASTLE UTD 1
1. Tim Krul
22. Daryl Janmaat
18. Chancel Mbemba
2. Fabricio Coloccini
43. Kevin Mbabu 53'
7. Moussa Sissoko 66'
8. Vurnon Anita
11. Yoan Gouffran 66'
5. Georginio Wijnaldum
45. Aleksandar Mitrovic
17. Ayoze Perez
Subs
6. Mike Williamson
9. Papiss Cisse
10. Siem de Jong
15. Jamaal Lascelles 53'
20. Florian Thauvin 66'
21. Rob Elliot
24. Cheick Tiote 66'
Sergio Aguero scored five goals in a sensational 20-minute spell as Manchester City came from behind to crush Newcastle 6-1 in the Barclays Premier League.
It was a stunning return to form from the Argentinian, who had scored just once from open play prior to this remarkable blitz against the Magpies at the Etihad Stadium.
Kevin de Bruyne also got on the scoresheet as City, after falling behind to an Aleksandar Mitrovic header during a laboured first-half display, powered back to the top of the table.
Aguero had gone into the game with question marks over his form after a recent knee injury and a patchy display against Borussia Monchengladbach in midweek.
But his late penalty winner in Germany clearly had a rejuvenating effect and for a sparkling period either side of half-time he was world class and unstoppable.
City were ragged and defended badly in the first half but their awakening after the break transformed the game and shredded all Newcastle's positive early work.
The visitors took the game to City in the first half, although they did have a let-off when Tim Krul palmed away a De Bruyne free-kick and Fernando twice failed to bundle the ball in.
City looked vulnerable out wide and Newcastle's 18th-minute opener came as they cut the hosts open down the left. Chancel Mbemba's initial cross was half-cleared by Eliaquim Mangala but Georginio Wijnaldum quickly returned the ball and Mitrovic headed in from six yards.
Mitrovic spurned a great chance to double the lead as he raced onto a Moussa Sissoko through-ball only to shoot straight at Joe Hart.
Newcastle boss Steve McClaren reacted by putting his head in his hands, as if he knew a great chance might have passed his side by.
But really it might have mattered little, as City pulled one back before the break and then powered away courtesy of Aguero.
Aguero first shot narrowly wide from the edge of the area but then made no mistake three minutes before the interval as thumped in a header after Fernandinho had nodded down David Silva's floated cross.
City then really picked up the pace after the break and Aguero struck again as he took a Silva pass in his stride and beat Krul with aid of a deflection off Yoan Gouffran.
He completed his treble just a minute later - his third goal in the space of just eight minutes' playing time - with a classy finish, delicately chipped over the advancing Krul from a near-perfect De Bruyne pass.
From a position of strength just before break, Newcastle were rocking and their capitulation continued.
De Bruyne made it 4-1 after 52 minutes by lobbing Krul with a brilliant volley on the turn from a cross from impressive substitute Jesus Navas wide on the right.
Moments later it was 5-1 as Aguero took a touch to wrong-foot Mbemba on the edge of the area from a Silva pass and clinically despatched a low curling shot beyond Krul's reach.
Aguero then became the fifth player in Premier League history to score five goals in a match just after the hour when he turned in a De Bruyne cross from close range.
It was a blistering purple patch from Aguero and it came as some surprise when he was taken off by manager Manuel Pellegrini after 66 minutes, replacing him with Wilfried Bony.
Bony and Kelechi Iheanacho both had late chances but the job had been done by City in comprehensive fashion and Newcastle were probably pleased to escape the field without further damage.
THE TOON'S GREATEST 100 PLAYERS ... EVER!
AMAZON: http://www.amazon.co.uk/The-Toons-Greatest-Players-EVER/dp/132629685X
Available from M&M News, in Newcastle.
This book is a collection of the 100 Greatest Newcastle United players of all time, as voted for by NewcastleUtd-Mad.co.uk readers and a panel of journalists who contribute to the website. The players are in an order of five-per-chapter, counting down from 100 to Newcastle United's greatest ever player (as viewed by the author), but the whole point of the book is for YOU (the reader) to decide who goes where. The list is not, by any means, definitive. As with all books of this nature, whether it be "Greatest Albums"; "Best Movies Of All Time"; or "Top 100 Pin-Ups Of The Year" ... no two people have exactly the same opinion. There will be controversy over who is on the list, and chances are, more controversy over who is not. Here are the best of the best. I have painted the picture with each player's profile. Where they end up in the league of NUFC's Greatest is up to you. Because YOU have the final word.
Otherwise ... if you want a signed copy (for a birthday, etc) for £9.95 and no postage ... you can meet me before a match and I will bring a copy along.
Get in touch: Kevnumad@fsmail.net
NEWCASTLE UNITED
Fri 10th July (8pm BST)
Gateshead FC 0 Newcastle Utd 1 (Cisse pen)
(First half): Darlow, Janmaat, Haidara, Lascelles, Williamson, Anita, Colback, Gouffran, Cisse, Sissoko, De Jong. (Second half): Woodman, Bigirimana, Satka, Good, Ferguson, Tiote, Obertan, Aarons, Perez, Armstrong, Riviere.
Tue 14th July (8pm CT)
Club Atlas (MEX) 2 Newcastle Utd 1 (Sissoko)
Krul (Darlow 46); Janmaat (Bigirimana 72), Williamson, Lascelles, Haidara (Ferguson 72); Anita, Colback; Sissoko (Obertan 72), de Jong (Perez 72), Gouffran (Aarons 72); Cisse (Armstrong 72).
Sat 18th July (8pm UTC)
Sacramento Republic FC (USA) 0 Newcastle Utd 1 (og)
Krul (Woodman 46), Janmaat, Williamson, Lascelles (Taylor 46), Haïdara, Anita, Colback, Sissoko, Obertan (Aarons 69), de Jong (Perez 69), Cissé (Wijnaldum 69).
Tue 21st July (7.30pm UTC)
Portland Timbers (USA) 4 Newcastle Utd 3 (Wijnaldum, Aarons 2)
Darlow (Woodman 46), Bigirimana, Satka, Ferguson, Aarons; Abeid (Anita 65), Wijnaldum (Janmaat 46), Gouffran (De Jong 76), Sissoko (Obertan 46), Ayoze, Cisse (Armstrong 46).
Sun 26th July (1pm BST)
Sheffield United 2 Newcastle Utd 2 (Wijnaldum, de Jong)
Krul, Janmaat, Williamson, Taylor (Lascelles 69), Haïdara, Anita (Obertan 59), Colback, Sissoko (Abeid 80), Wijnaldum (De Jong 73), Perez (Aarons 45), Cissé (Armstrong 80)
Wed 29th July (7.45pm BST)
York City 2 Newcastle Utd 1 (Perez)
Darlow (Elliot HT); Bigirimana, Lascelles, Satka, Ferguson; Abeid, Gouffran; Aarons (Kemen 59), De Jong, Perez; Mitrovic (Suddick 70)
Sat 1st August (3pm BST)
Newcastle Utd 0 Borussia Mönchengladbach 1
Krul, Janmaat (Mbemba 62), Williamson, Taylor, Haïdara, Anita (De Jong 75), Colback, Sissoko (Perez 81), Obertan (Aarons 62), Wijnaldum, Cissé (Mitrovic 62).
Sunday August 9
NEWCASTLE UTD 2 SOUTHAMPTON 2 (Cisse, Wijnaldum)
Krul, Janmaat, Mbemba, Coloccini, Haidara; Colback, Anita (Tiote, 67); Sissoko, Wijnaldum (De Jong, 81), Obertan; Cisse (Mitrovic, 75). Subs not used: Darlow, Taylor, Aarons, Perez.
Saturday August 15
SWANSEA CITY 2 NEWCASTLE UTD 0
Krul, Janmaat, Mbemba, Coloccini, Haidara, Anita, Colback, Sissoko (45' Taylor), Wijnaldum, Obertan (82' Mitrovic), Cisse (54' Aarons). Subs: Williamson, Perez, Tiote, Darlow
Saturday August 22
MANCHESTER UTD 0 NEWCASTLE UTD 0
Krul, Mbemba, Taylor, Coloccini, Haidara, Anita, Colback, Perez (78' Tiote), Wijnaldum, Obertan (69' Thauvin), Mitrovic (88' Cisse).
Subs: Williamson, de Jong, Aarons, Darlow
Tuesday August 26
NEWCASTLE UTD 4 NORTHAMPTON TOWN 1 (Thauvin, Janmaat, de Jong, Williamson
Darlow, Janmaat, Lascelles, Williamson, Haidara (78' Toney), Tiote, Gouffran, Aarons, de Jong, Thauvin (65' Mitrovic), Perez (72' Colback).
Subs: Dummett, Wijnaldum, Mbemba, Elliot.
Saturday August 29
NEWCASTLE UTD 0 ARSENAL 1
Krul, Janmaat, Mbemba, Coloccini, Haidara, Anita (72' Perez), Sissoko (78' Cisse), Wijnaldum, Thauvin (87' de Jong), Mitrovic
Subs: Obertan, Tiote, Darlow, Taylor
Monday September 14
WEST HAM UTD 2 NEWCASTLE UTD 0
Krul, Janmaat, Mbemba, Coloccini, Haidara, Anita (60' de Jong), Colback, Sissoko, Wijnaldum (79' Aarons), Thauvin (60' Perez), Cisse Subs: Gouffran, Obertan, Lascelles, Darlow
Saturday September 19
NEWCASTLE UTD 1 WATFORD 2
Krul, Janmaat, Mbemba, Coloccini, Haidara (80' Aarons), Wijnaldum, Colback, Thauvin (88' Obertan), Sissoko, Perez, Cisse (45' de Jong)
Subs: Williamson, Anita, Lascelles, Elliot
Wednesday September 23
NEWCASTLE UTD 0 SHEFF WED 1 (League Cup)
Krul, Janmaat (45' Mbabu), Lascelles, Williamson, Mbemba, Anita, Wijnaldum, Thauvin (45' Perez), Sissoko, Obertan (71' Toney), de Jong
Subs: Coloccini, Gouffran, Elliot, Barlaser
Saturday September 26
NEWCASTLE UTD 2 CHELSEA 2 (Perez, Wijnaldum)
Krul, Janmaat, Mbemba, Coloccini, Mbabu, Sissoko (90+2' de Jong), Colback (54' Obertan), Anita, Wijnaldum, Perez, Mitrovic (85' Toney)
Subs: Williamson, Lascelles, Thauvin, Elliot
Saturday October 3
MANCHESTER CITY 6 NEWCASTLE UTD 1 (Mitrovic)
Krul, Janmaat, Mbemba, Coloccini, Mbabu (53' Lascelles), Sissoko (66' Tiote), Anita, Gouffran (66' Thauvin), Wijnaldum, Mitrovic, Perez
Subs: Williamson, Cisse, de Jong, Elliot
Sunday October 18
16:00 Newcastle United v Norwich City
Sunday October 25
12:00 Sunderland v Newcastle United
Saturday October 31
15:00 Newcastle United v Stoke City
Saturday November 7
12:45 Bournemouth v Newcastle United
Saturday November 21
15:00 Newcastle United v Leicester City
Saturday November 28
15:00 Crystal Palace v Newcastle United
Sunday December 6
16:00 Newcastle United v Liverpool
Sunday December 14
16:00 Tottenham v Newcastle United
Saturday December 19
17:30 Newcastle United v Aston Villa
Saturday December 26
17:30 Newcastle United v Everton
Monday December 28
15:00 W Brom v Newcastle United