Heaslip came off the bench in Edinburgh to score the only try of the match in Ireland's 22-15 victory over Scotland last weekend and reclaims the No 8 jersey from Denis Leamy.
That is one of the three changes coach Declan Kidney has made as Ireland go in search of only their second Grand Slam title to go alongside the one notched up 61 years ago.
Ireland have won three of the four matches played at the Millennium Stadium since the Five Nations became Six and, on top of their four-from-four record so far this time around, they also boast a superior points advantage over Wales.
In a second change to the pack, Jerry Flannery returns to the starting hooker's position after featuring as a second-half replacement against Scotland for his fourth start of the championship, with Rory Best reverting to the bench for the game.
The final change is at scrum-half, with Tomas O'Leary coming back into the side and swapping places with Peter Stringer.
"The difference between the players is so small," said Kidney.
"The changes were partly for tactical reasons. It's about getting the right chemistry."
Robert Kearney (UCD - Leinster); 14 - Tommy Bowe (Ospreys), 13 - Brian O'Driscoll (UCD - Leinster, captain), 12 - Gordon D'Arcy (Lansdowne - Leinster), 11 - Luke Fitzgerald (Blackrock College - Leinster); 10 - Ronan O'Gara (Cork Constitution - Munster), 9 - Tomas O'Leary (Dolphin - Munster); 1 - Marcus Horan (Shannon - Munster), 2 - Jerry Flannery (Shannon - Munster), 3 - John Hayes (Bruff - Munster), 4 - Donncha O'Callaghan (Cork Constitution - Munster), 5 - Paul O'Connell (Young Munster - Munster), 6 - Stephen Ferris (Dungannon - Ulster), 7 - David Wallace (Garryowen - Munster), 8 - Jamie Heaslip (Naas - Leinster)
Replacements: 16 - Rory Best (Banbridge - Ulster), 17 - Tom Court (Malone - Ulster), 18 - Mick O'Driscoll (Cork Constitution - Munster), 19 - Denis Leamy (Cork Constitution - Munster), 20 - Peter Stringer (Shannon - Munster), 21 - Paddy Wallace (Ballymena - Ulster), 22 - Geordan Murphy (Leicester)