The Poland international was injured following a late challenge on his left knee by defender Antony Kay in Tuesday's 2-1 away win at MK Dons.
Following an initial scan, the 23-year-old forward is now facing surgery.
"If he gets back in under a year, he'll have done well," Wolves head of medical Phil Hayward told BBC WM.
"He's really looking at a full year and maybe more than that.
"He has suffered damage to both the cruciate and lateral knee ligaments, as well as other structural damage. There is a small fracture on the inside of the knee, indicative of the amount of force involved in the challenge.
"He will see a consultant this week and undergo surgery once the swelling has subsided at some point in the next two weeks. The timeframe will become more apparent following surgery. But he is expected to be out for a considerable time."
MK Dons defender Kay was yellow carded for the challenge by match referee Mark Heywood.
Zyro is the third Wolves player to suffer a serious knee injury this season.
Striker Nouha Dicko has been sidelined since August, while winger Jordan Graham was then himself ruled out for up to nine months in January.
Wolves have also lost winger Razak Boukari and defender Ethan Ebanks-Landell for the season, while centre-half Mike Williamson (thigh injury) has not figured since returning to the club from Newcastle United in January.
Since Christmas, they have also spent long spells without Zyro, who missed two months with a calf injury, James Henry, Dave Edwards and Jed Wallace.
Henry made his first start since February in midweek, while Wales international Edwards made a late appearance from the bench.
Wolves head coach Kenny Jackett has cleared up confusion over midfielder Kevin McDonald's whereabouts.
It was reported that the 27-year-old Scot had been told to "train with the kids" after being left out of Jackett's matchday squad of 18 at MK Dons.
But McDonald actually voluntarily chose to keep fit with Wolves' Under-18 side. They were the only ones in training, because the Under-21 team also had a game on Tuesday.
McDonald, Wolves' player of the year in 2013-14 when they won the League One title, has not made the starting line-up since 8 March and has been linked with an end-of-season move to Scottish Championship winners Rangers.
Wolves boss Kenny Jackett and head of medical Phil Hayward were speaking to BBC WM's Rob Gurney.

The mural, called Slave Labour, disappeared from a wall in Wood Green, north London, in February and appeared in a Miami sale.
But it was removed from the lot after protests by Haringey Council.
It is now up for auction in June in Covent Garden by the Sincura Group. A local councillor and the local Trades Union Congress have attacked the sale.
The mural, which depicts a boy hunched over a sewing machine making Union Jack bunting, appeared on the side of a Poundland store last May, just before the Diamond Jubilee celebrations.
A spokesman for the auctioneers Sincura said the mural "has been sensitively restored under a cloak of secrecy", and will go on show alongside pieces by Damien Hirst, Andy Warhol, Mario Testino and Russell Young.
But Wood Green councillor Alan Strickland said: "This is a piece of art given to the community for public enjoyment, and people will find it galling that you can only view this work at an expensive champagne reception, when it belongs with the people of north London, not a private owner.
"We saw the level of public anger last time, as the story went around the world, and I expect the same this time."
And Keith Flett, secretary of the Haringey Trades Union Congress, said: "The Slave Labour Banksy belongs to the people of Haringey not to a wealthy private client."
When the mural was up for auction in Miami, it was expected to fetch up to Â£450,000.
There was suspicion it had been stolen when it disappeared but the Metropolitan Police said there were "no reports of any theft".
Slave Labour will go on sale at the London Film Museum on 2 June.
Injury-hit Wolves have suffered a new blow with the loss of Michal Zyro for potentially more than a year with multiple knee ligament damage.
[NEXT_CONCEPT]
A Banksy artwork which had been withdrawn from an auction in the US has been put up for sale again.