Holloway followed seven changes for Saturday's win against Plymouth with another seven against the Blades on Tuesday night.
Up to half-time it looked as if Holloway's system might have rebounded as injury-hit United began to take a grip on the game - with striker Darius Henderson twice forcing full-length saves from Matt Gilks.
But he brought on internationals David Vaughan and Charlie Adam at the break, and that turned the tables on Kevin Blackwell's team.
"I always try to make changes, because I believe I have now got a squad with strength in depth," Holloway explained.
"We did suffer a bit in the first half against Sheffield, who are a big physical side.
"But the new lads took us in 0-0 - and when the new people came on it made a difference. We had weathered the storm and knew we could step up a gear."
Holloway was unsighted for his team's opening goal, on the hour.
"I was delighted Marcel Seip got his second goal for us - but I have to admit I missed it, because I had to go to the toilet," he reported.
"All I could hear was the roof coming off the stand, with the crowd's noise.
"I will carry on with my policy of making changes - because each match in the Championship is horses for courses."
Holloway's opposite number Blackwell had less to smile about.
"We are going through a bad time, but I feel our work ethic is good and I'm not having people say there is no spirit in the side," he said.
"Things did just not go for us when it mattered. I thought we were the better side in the first half. But the first goal made the difference, and Blackpool got on top.
"There are excuses. I have got injuries, and new players are fitting in. But things will start to happen for us, and I'm not worried."
The Blades started with a long-ball game in difficult, blustery conditions. That tactic had little to show for it, and they joined Blackpool with short passes.
There were few chances in the first half.
The most dangerous moments came from runs down the flank by Blackpool wing-back Neal Eardley, whose inch-perfect crosses found Jason Euell lurking in the box.
But the veteran striker had one effort narrowly wide and two others blocked by defenders.
Blackpool eventually went ahead when a Vaughan corner found Seip hurtling in at the back post, and the Dutchman's header powered past Mark Bunn from 12 yards.
Fellow centre-back Alex Baptiste went close from two more Vaughan corners, before Blackpool increased their lead on 69 minutes.
Eardley fired a cross low into the box - and this time Euell was on target, steering home from seven yards.
An audacious lob from Adam almost caught out Bunn from 45 yards.
Then Adam made no mistake on 81 minutes when he was set up by on-loan Arsenal youngster Jay Thomas and beat Bunn with a powerful low drive from the edge of the penalty area.