Ireland back-row Prendergast to make first Test start against England
The Connacht back-row's previous two caps have come off the bench but the forceful Caelan Doris was instead named among the replacements when coach Andy Farrell named his matchday 23 on Thursday.
Farrell, whose side sit top of the global rankings just weeks away from next month's start of the World Cup in France, has recalled 11 of the team which clinched a Six Nations Grand Slam against England in March.
Centre Garry Ringrose and lock Tadhg Beirne, both injured for that 29-16 win, and fly-half Ross Byrne join Prendergast in the starting XV, with Munster wing Keith Earls set to win his 100th cap should he come off the bench.
Prendergast took the field in the first half of Ireland's 33-17 win over Italy on August 5 following an injury to Jack Conan.
With Conan still out with a foot issue, the 23-year-old has a chance to provide competition for the influential Doris, man of the match with two tries against the Azzurri.
In the ongoing absence of suspended captain Johnny Sexton, Leinster team-mate Byrne has another chance to impress at fly-half, He will be partnered by scrum-half Jamison Gibson-Park.
Farrell has selected his first-choice front row of Andrew Porter, Dan Sheehan and Tadhg Furlong, with captain James Ryan and Beirne at lock and reigning world player of the year Josh van der Flier and Peter O'Mahony either side of international novice Prendergast.
Earls is on the cusp of becoming just the ninth Irelanmd international to win 100 caps following Brian O'Driscoll, Ronan O'Gara, Cian Healy, Rory Best, Sexton, Paul O'Connell, John Hayes and Conor Murray.
Former England dual-code international Farrell is set to name his final 33-man squad for the World Cup on August 28.
Ireland team to play England (15-1)
Hugo Keenan; Mack Hansen, Garry Ringrose, Bundee Aki, James Lowe; Ross Byrne, Jamison Gibson-Park; Cian Prendergast, Josh van der Flier, Peter O'Mahony; James Ryan (capt), Tadhg Beirne; Tadhg Furlong, Dan Sheehan, Andrew Porter
Replacements: Rob Herring, Jeremy Loughman, Finlay Bealham, Joe McCarthy, Caelan Doris, Conor Murray, Jack Crowley, Keith Earls
Coach: Andy Farrell (ENG)