The Wildcats (19-1, 4-1 Southeastern Conference) moved atop the rankings for this week for the first time since 2003. They were cautioned by no less a fan than President Barack Obama earlier Tuesday to keep their focus and play with the same passion that brought them to the top.
The president or Kentucky didn't count on Downey, the SEC's leading scorer to break the 30-point mark for the fourth time in six league games for South Carolina (12-8, 3-3).
The Gamecocks had lost all seven previous games they'd played against No. 1-ranked teams.
DeMarcus Cousins matched his career best of 27 points to lead Kentucky, which had been the nation's last unbeaten team.
Fans rushed the Colonial Life Arena floor when the buzzer sounded, Downey hugging whomever he could and screaming, "I told you so!"
Downey had seemingly hit a game-winner at Florida on Saturday, scoring on a driving layup with 5 seconds left until the Gators' Chandler Parsons outdid him with a winning 3-pointer.
This time, though, Downey and the Gamecocks would not be stopped - even after the Wildcats fabulous freshmen of John Wall and Cousins seemed to take things over.
The pair combined for 13 points during a 14-3 run midway through the second half that put the Wildcats up 47-42. That's when Downey took over.
South Carolina's senior had a three-point play and two foul shots to tie it up.
Downey had another three-point play with 4:06 left to give the Gamecocks the lead for good at 54-51.
Wall's three-point play with 40.1 seconds left brought Kentucky within 62-61. But Brandis Raley-Ross followed with two free throws to restore the edge.
Raley-Ross finished with 17 points.
Cousins had 12 rebounds to go along with his points, which tied his best performance set earlier this season against Seton Hall.
Kentucky was on its longest win streak to start a season in 44 years and figured to continue its roll against depleted South Carolina.
But the game followed a head-in-the-clouds moment earlier Tuesday when President Obama called to congratulate Coach John Calipari and the players for helping raise more than $1 million for Haitian relief.
Along with the praise came Obama's caution - stay focused Wildcats or bad things might happen.
The president's words were prophetic.
The Wildcats were ragged and out of sync. Wall, who Obama greeted with "What's going on all-star?" when they spoke by phone, was 6 of 16 from the field with four of Kentucky's 15 turnovers.
Wall ended with 19 points.
No Wildcat could corral Downey.
While the Gamecocks' senior didn't have his shooting touch (9 of 29), he went 10 of 11 at the free throw line.