Ulster scrumhalf John Cooney will make his full Ireland debut against USA on Saturday.
Having had some cameo performances off the bench, head coach Schmidt has handed him a long awaited start against the currently unbeaten North Americans.
He is partnered with Joey Carberry in the half back positions.
Tadhg Beirne has a chance to kick-start his Test career also winning selection in a much-changed Ireland team from that which defeated New Zeawland last week.
Garry Ringrose is the sole survivor from that stunning 16-9 win over New Zealand, Schmidt making 14 changes for the USA’s visit to Dublin.
Munster lock Beirne will earn his fourth cap and second start, while his provincial team-mate Sam Arnold could make his Test debut off the bench.
Beirne is quickly advancing his Ireland claims after trading Scarlets for Munster in the summer, and has already put some heat on senior locks like Iain Henderson and Devin Toner.
Toner excelled in Ireland’s first-ever victory over New Zealand on home soil though, to reassert his status as starting lock, alongside the ever-imperious Leinster youngster James Ryan.
Henderson will be itching to prove a point given he is starting against the USA then, having not made the starting line-up for the All Blacks win.
Head coach Schmidt confirmed he had always planned to make wholesale changes for the USA clash, then hailed lock Beirne’s swift progress in the Ireland set-up.
“This was always part of the plan to make the changes, the two games book-ended the series and it’s a chance to look at all of the 43 players across the four matches,” said Ireland boss Schmidt.
“Tadhg (Beirne) has slotted in so well, coming off the bench a couple of times in Australia in the summer, and bedding in as part of the broader squad.
“And I thought Iain Henderson came on and did really well last week against New Zealand.
“Tadhg has a really instinctive feel for the game; his running lines, his ability to get into the right defensive positions. Those things are a little bit intuitive, and it’s great to coach a guy who tends to know where to be most of the time.”