Gregor Townsend has made nine personnel changes to the team that beat the Ospreys 35-17 at Scotstoun last month, for the final game of the regular season.
There are also two positional switches from the team that secured their play-off place against the defending champions, with only Sean Lamont, Pat MacArthur, Moray Low, Tim Swinson, Rob Harley and John Barclay remaining in the starting XV.
British & Irish Lions pair Stuart Hogg and Sean Maitland drop to the bench, along with Glasgow's player of the season Niko Matawalu, Ryan Grant and Josh Strauss.
Alex Dunbar, Graeme Morrison, Duncan Weir and Al Kellock drop out of the squad altogether for the trip to Galway.
Gregor Townsend said: "We were delighted with our performance against the Ospreys which secured our play-off spot, but we know we'll face a big challenge tomorrow night at a ground we've not won at since 2007.
"Connacht are enjoying a great run of form at the moment, having lost just twice in their last seven games, so it will be an extremely tough game for us, but one we're all looking forward to."
Peter Murchie comes in at full-back in place of Hogg, Tommy Seymour replaces Maitland on the right wing and the club's equal all-time top try scorer DTH van der Merwe comes in on the opposite side, with Sean Lamont moving to outside centre in place of Alex Dunbar.
Peter Horne replaces Morrison at inside centre, Ruaridh Jackson comes in for the injured Weir at fly half and Henry Pyrgos replaces Matawalu at scrum half.
In the pack Moray Low moves from tight head to loose head in place of Grant, with Jon Welsh coming in at tight head and Pat MacArthur continuing at hooker.
Club captain Al Kellock drops out of the squad for the trip to Ireland as his wife has just given birth, so Tim Swinson and Tom Ryder combine in the second row.
Ryan Wilson is given the captaincy and comes in at number eight, with Rob Harley continuing at blind-side and John Barclay keeping his place at open-side.
Glasgow have Dougie Hall, Ryan Grant, Ed Kalman, James Eddie, Josh Strauss, Niko Matawalu, Sean Maitland and Stuart Hogg on the bench.
The Warriors are third in the RaboDirect PRO12, one point behind second-placed Leinster and four points behind leaders Ulster.
Glasgow are looking for their first win on the road since beating Newport Gwent Dragons 60-3 at Rodney Parade in February, but have not won at the Sportsground since 2007.
Townsend said: "With a couple of players out injured, it is an opportunity for others to stake a claim to be selected for our semi-final. It's a new halfback and midfield combination and we expect a high workrate and accuracy from them. I am also looking forward to seeing Tommy Seymour and Peter Murchie back in a Warriors jersey. They both performed well the last time we played in Ireland in our narrow defeat to Leinster, and have trained very well the past two weeks."
"It's an exciting time for the club with the selection of two British Lions and our play-off place secured, but our focus is all about meeting the challenge of Connacht and delivering a top performance."
Glasgow Warriors team to play Connacht in Round 22 of the RaboDirect PRO12, Sportsground, Friday 3 May (kick-off 7.45pm):
15 Peter Murchie
14 Tommy Seymour
13 Sean Lamont
12 Peter Horne
11 DTH Van der Merwe
10 Ruaridh Jackson
9 Henry Pyrgos
1 Moray Low
2 Pat MacArthur
3 Jon Welsh
4 Tim Swinson
5 Tom Ryder
6 Rob Harley
7 John Barclay
8 Ryan Wilson (C)
16 Doug Hall
17 Ryan Grant
18 Ed Kalman
19 James Eddie
20 Josh Strauss
21 Niko Matawalu
22 Sean Maitland
23 Stuart Hogg
Not available for selection through injury:
M Cusack (shoulder), C Cusiter (shoulder), A Dunbar (hip), C Fusaro (groin), F Gillies (neck), D Weir (ankle).
Guinness PRO12
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