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The Northern Irishman will tee off at Brookline Country Club buoyed by clinching the 21st PGA Tour crown of his career in Ontario last weekend.
Two-time major winner Lyle expects McIlory to be brimming with confidence going into the showpiece tournament in Massachusetts, which begins on Thursday.
“US Open’s are tough but McIlroy, obviously winning in Canada, that couldn’t have happened at a better time for him,” Lyle told the PA news agency.
“He needed that boost. You can’t go into a drug store and buy that boost of energy, of confidence, it has to be earned and that’s through winning.
“And that’s what he did really well, he looked like he enjoyed it. If I was going to put money down, I’d pick McIlroy right now because of momentum of winning.
“(Scottie) Scheffler would be right behind and Dustin Johnson would be next.”
McIlroy, 33, previously won the US Open in 2011.
The build-up to the 122nd edition, which runs until Sunday, has been dominated by discussions about the LIV Golf tour.
The controversial £200m Saudi Arabian-funded invitational series started last week at the Centurion Club in Hemel Hempstead.
Four-time major winner McIlroy opposes the rebel circuit and has expressed disappointment at players who have made U-turns to join, while also reiterating his commitment to the PGA Tour.
Despite that stance, Lyle – who won the Open Championship in 1985 and the Masters three years later – believes McIlory would be the top target for LIV organisers seeking further high-profile recruits.
“He might be the one that would be hit with the Saudi thing, the carrot under your nose, money-wise – and Tiger (Woods) as well,” said the 64-year-old Lyle.
“He would be the number one that they would want – they would want someone like Rory McIlroy to play. But I think he’s looked at all the ins and outs, and the dos and don’ts and the don’t knows – there are a lot of don’t knows.
“Yes, there’s big money. But there are a lot of don’t knows in the longevity of it, how it’s going to unfold.
“It’s a bit like a court case, it could go on for another year, it could go on for another five years. We don’t know the outcome.”
Sandy Lyle is supporting The 150th Open Championship Claret Jug Tour, in partnership with HSBC UK. The tour will visit schools, golf clubs, city centres and HSBC branches across the UK and Ireland, finishing at St Andrews for The 150th Open in July