Ashton, who made the summer switch from Northampton, is the only new face in the line-up after Alistair Hargreaves picked up an injury in the build-up to the match.
Owen Farrell also suffered a knock in training, so Charlie Hodgson starts at fly-half with Joel Tomkins teaming up with Brad Barritt in the centres.
Mako Vunipola and Petrus du Plessis join Schalk Brits in the front-row, while there is a welcome return to action for Kelly Brown following a lengthy spell out.
"It promises to be an exciting season in the Aviva Premiership and looking around the league, all clubs have strengthened going into the new campaign with quality players joining from all across the globe - proving that this competition is one of the best in the world," said director of rugby Mark McCall.
"The players have worked hard over the summer months in an excellent pre-season that has allowed us to spend time together on and off the field, creating an even stronger bond among the group.
"The objective of the club is to be consistently successful and we are aware that in order for that to be achieved, there will be no substitute for hard work over the coming months - starting at Twickenham on Saturday.
"London Irish have made a number of changes on and off the field. In Brian Smith they have an experienced director of rugby and with the likes of Tomas O'Leary and Shane Geraghty joining their squad, they have also added quality on the pitch which should make for an exciting game."
New Zealand lock Bryn Evans has been handed the London Irish captaincy as Declan Danaher starts the match on the bench.
Evans will partner new signing George Skivington in the second row, with Scott Lawson and Tomas O'Leary also making their debuts.
There is also a start for Jon Fisher, who returns to the club after a season at Bedford, while fellow summer arrivals Halani Aulika, Cai Griffiths and Shane Geraghty named on the bench.
"We've got a fantastic squad on board for the 2012/13 season and we are looking forward to the season ahead," said Smith.
"This squad is very ambitious and we aim to emulate the deeds of our courageous sevens team that won the JP Morgan sevens title over the summer."
Saracens: 15 Alex Goode, 14 Chris Ashton, 13 Joel Tomkins, 12 Brad Barritt, 11 Chris Wyles, 10 Charlie Hodgson, 9 Richard Wigglesworth, 8 Ernst Joubert, 7 Will Fraser, 6 Kelly Brown, 5 Mouritz Botha, 4 Steve Borthwick (c), 3 Petrus du Plessis, 2 Schalk Brits, 1 Mako Vunipola.
Replacements: 16 Jamie George, 17 Rhys Gill, 18 Carlos Nieto, 19 Eoin Sheriff, 20 Jackson Wray, 21 Neil de Kock, 22 Nils Mordt, 23 James Short.
London Irish: 15 Tom Homer, 14 Topsy Ojo, 13 Jonathan Joseph, 12 Sailosi Tagicakibau, 11 Marland Yarde 10 Steve Shingler, 9 Tomás O'Leary, 8 Jon Fisher 7 Ofisa Treviranus, 6 Jamie Gibson, 5 Bryn Evans (c), 4 George Skivington, 3 Leo Halavatau, 2 Scott Lawson, 1 Max Lahiff.
Replacements: 16 Brian Blaney, 17 Halani Aulika, 18 Cai Griffiths, 19 Kieran Low, 20 Declan Danaher, 21 Alex Gray, 22 Shane Geraghty, 23 Jack Moates.
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