Roy, who impressed against the white ball in the World Cup, is set to open the batting alongside Rory Burns.
Joe Root captains the side but will not have James Anderson in his ranks with the bowler missing out due to a calf injury.
There is also a debut for Olly Stone, who is back fit having been forced to return home early from England’s tour of the Caribbean earlier this year.
Lewis Gregory is the other man from England’s initial 13-man squad to miss out with the Three Lions opting for two spinners.
A number of England’s World Cup stars are being rested for this Test with the Ashes getting underway on August 1.
Though with the Three Lions having an unsettled top order, the clash at Lord’s provides a big opportunity for Roy.
He will face the new ball alongside Surrey team-mate Rory Burns, though Roy does not open for his county in the Championship.
And former England star Mark Ramprakash worries that there may be too much pressure on the 29-year-old.
He said: “My worry would be expectation of the public.
“If we go too hard that would be a little unfair on Jason.
“I don’t think England have a lot of options. I have sympathy for the selectors because there haven’t been many people scoring very heavily in county cricket.
“Jason has a really exciting challenge in front of him and that is to retain his aggressive intent and the way he wants to play.
“He plays like that in four-day cricket and he has made runs in recent years in the little four-day cricket he has played.
“What he has done really well when he has made those runs is be clinical in his execution of his attacking shots, but he has got a decent defence as well.
“I think he is the outstanding candidate – I wish there were a few more putting pressure on to say ‘pick me’ for those top-order places because it has been an area where we have struggled.”
For Anderson, the hope will be that he is fit enough to face Australia in nine days time.
England’s record Test wicket-taker sustained a calf injury playing for Lancashire against Durham on 2 July.
He had been named in the initial squad to face Ireland but now misses out.
England team vs Ireland: Joe Root (c), Moeen Ali, Rory Burns, Jonny Bairstow, Stuart Broad, Sam Curran, Joe Denly, Jack Leach, Jason Roy, Olly Stone, Chris Woakes.