Scans showed champion flanker Pocock suffered a torn anterior cruciate ligament (ACL) playing for the Brumbies in their 35-6 Super Rugby drubbing of the NSW Waratahs at Canberra Stadium.
Rated as the premier openside flanker in the world by his Brumbies replacement George Smith, Pocock was hurt when falling awkwardly in a tackle by fellow Wallaby Adam Ashley-Cooper.
He faces a knee reconstruction and is set to miss the three-Test Lions series starting in June and the Wallabies' entire Rugby Championship campaign as well as the rest of the Super Rugby season.
Pocock was contending to be coach Robbie Deans' choice to skipper the Wallabies this year.
Injuries last year forced Deans to switch the captaincy from James Horwill to Pocock, then Will Genia and the now-retired Nathan Sharpe and he had acknowledged the choice this year was between Pocock and Horwill.
Replacing Pocock at openside flanker will also be a big task but fortunately there are some impressive contenders, notably the Waratahs' Michael Hooper and the Queensland Reds' Liam Gill.
And Wallabies great Smith, a veteran of 110 Tests, could now emerge as a contender after replacing the injured Pocock on the field for the Brumbies in his comeback to Super Rugby on Saturday.
His experience would be invaluable in the pressure-cooker atmosphere of a Lions series.
However, Smith's Test availability is not clear as he is still contracted to a Japanese club and only playing for the Brumbies on a short-term deal in their off-season.
Hooper made a big impression when playing most of the 2012 Tests for the Wallabies after Pocock suffered a cartilage injury to his other - right - knee, ruling him out till late in the end of season tour to Europe.
Brumbies captain Ben Mowen said the loss of Pocock was extremely disappointing, but more so from a personal point of view.
"You invest a lot in your playing group and the friendships that you build and you really do ride the highs and lows with each other," said Mowen.
"But in saying that he's an absolute quality guy and if anyone's going to do the recovery right ... he's going to be the guy who's going to do it."
Brumbies coach Jake White was not denying how fortunate it was the Brumbies had signed Smith recently to play most of the Super Rugby tournament.
"It shows you how fate plays out ... it's just fantastic how things have worked out now that George has arrived," White said.
"It's not nice on Poey, but at the same time it just shows how important depth is in this competition and when you have depth like George it's even better."
There were no other injuries for the Brumbies in their third consecutive win for the season and loose-head prop Ben Alexander avoided being cited for stomping on Benn Robinson despite receiving a yellow card in the 69th minute.
Hooker Tatafu Polota-Nau, who went off with a hamstring concern not long after Pocock, is the only injury concern for the Waratahs and the full extent of the strain will be revealed on Monday.
Polota-Nau's absence arguably had a bigger impact on the game than that of Pocock's with the Waratahs lacking his defensive flair and failing to secure ball at the lineout.
The Waratahs will need to quickly regroup before facing a buoyant Cheetahs side at Allianz Stadium in just six days time, while the Brumbies fly out to Durban to take on the Sharks early next Sunday morning (AEDT) in the first leg of their two-week South African tour.