In a third-round shock of sorts, League One Saints overcame top-flight opposition thanks to second-half goals from Lee Barnard and Guly Do Prado.
But Holloway had virtually written off his side's chances in the competition beforehand, and made nine changes to his starting line-up with half the youth team making up the bench.
Holloway makes no bones about the fact survival in the Premier League is his sole focus, so his established stars did not even make the trip south.
In fairness to the Seasiders boss, it says everything about their recent achievements that their squad looks so lightweight even when compared to a third-tier side, who made eight changes themselves but still managed to field a line-up of first-team regulars.
All Holloway wanted to see was his side give a good account of themselves and for the most part they did, especially in the second half.
The visitors almost equalised Barnard's opener - even if a replay was the last thing Holloway wanted - but Saints keeper Bartosz Bialkowski pulled off a fine save to deny Matt Phillips.
Southampton's priorities also lie elsewhere - they currently sit second in League One - but boss Nigel Adkins still included Adam Lallana the day after he signed a new four-and-a-half year contract.
The former England Under-21 international latched onto Jason Puncheon's through-ball only to chip over, and also fired a 20-yard effort inches too high in a lively opening for Saints. Seasiders keeper Paul Rachubka, making his first start in a year, had a stroke of luck when he spilled a Rickie Lambert shot but managed to grab the ball before Barnard arrived.
And there was mild controversy when Rachubka went to clear the ball only for Barnard to cheekily nod it out of his hand and put it into the net. However, referee Danny McDermid was having none of it and ruled the goal out.
Rachubka showed a safer pair of hands when he got down well to hold onto Lambert's deflected free-kick on the half-hour. And Saints blew a golden chance to take the lead three minutes later when, in an almighty goalmouth scramble, Rachubka palmed the ball to the feet of Lambert only for the striker to crash his shot against the crossbar from all of six yards out.
Rachubka also saved Barnard's header, blocked an attempted lob from Puncheon and kept out Lallana's low drive as a one-sided first half drew to a close.
Blackpool finally created a chance on goal two minutes into the second period, and former Saint Jason Euell really should have scored. Full-back Neil Eardley overlapped down the right and swung in an inviting cross but Euell wastefully headed over the top.
But Saints finally made the breakthrough six minutes minutes later after Lallana played in Lambert.
His effort was blocked by the foot of the onrushing Rachubka but the ball fell to Barnard, who steadied himself before crashing his shot past two defenders on the line.
To their credit, Blackpool attempted to hit back and were only denied by a stunning, full-length save from Bialkowski as he tipped a curler from Phillips wide.
Saints defender Aaron Martin also had to clear from underneath the crossbar as another Saints old boy, Brett Ormerod, attempted to force a loose ball home. At the other end Rachubka made fingertip saves to deny Barnard and Ryan Dickson.
But Brazilian substitute Do Prado put the icing on the cake with a sensational second two minutes from time, cutting inside on his right foot and rifling the ball past Rachubka from 20 yards.
There was even time for another sub, Liverpool target Alex Chamberlain, to smash a shot against the post as the Seasiders were sent packing.
Southampton 2-0 Blackpool: Match Report - view commentary, squad, and statictics of the game as it happened.