West Indies, overwhelmed 3-0 in the preceding Test campaign, were a team transformed and dominated England in all departments during Sunday's match.
They made 289 for five after Gayle - leading the side in the absence of the injured Ramnaresh Sarwan - backed up his decision to bat first after winning the toss with 82 in an innings featuring 82 not out from Runako Morton.
West Indies then built on that foundation with fast bowler Daren Powell, who finished with four for 40 and the man-of-the-match award, reducing England to 33 for three inside nine overs.
Powell's haul included having star batsman Kevin Pietersen out for nought.
Even more heartening, looking longer term, was that West Indies won without a major contribution from man-of-the-series Shivnarine Chanderpaul, who averaged 202 over the three games but was out for 33 on Sunday.
"I am very happy," Gayle told reporters after stumps. "I have to give thanks to the guys and the management team. I thought it was a tremendous effort and it means a lot to me, not only because I am the captain.
"Even if I was just a player and Ramnaresh Sarwan was here as the captain, it would still mean a lot to me.
"The vibes and the feeling out there was so good," added Gayle, whose appointment as skipper was initially queried by the West Indies Cricket Board, keen to go with replacement Test skipper Daren Ganga instead.
"There is a great spirit. We do a lot of planning and all the guys communicate well with each other."
A series win looked some way off after Sunday's 79-run loss at Lord's. But West Indies, on the back of Chanderpaul's 116 not out, levelled with a 61-run win at Edgbaston on Wednesday before wrapping up the series with more than five overs to spare at Trent Bridge.
"All the guys deserve this. We spoke about hitting the ground running today (Sunday) from ball one and we did that.
"To come from 1-0 down to win 2-1 is tremendous," added Gayle, whose side now travel to Dublin for a quadrangular one-day tournament.
Paul Collingwood, England's new one-day captain, admitted there was still plenty for his side to learn when it came to the shorter form of the game.
"We readily admit we've got a lot of work to do to become a top one-day side," said Collingwood of an England team that, like hosts West Indies, failed to reach the semi-finals of the recent World Cup.
"But, as long as we learn from this series, that is how we will move forward," added the all-rounder, whose team remained seventh in the International Cricket Council (ICC) one-day rankings compared to West Indies' eighth. "West Indies played fantastic cricket and you have to give them credit."
West Indies again cut loose in the last 10 overs at Trent Bridge, scoring 116 runs, having added 102 during the same period at Edgbaston.
Medium-pacer Dimitri Mascarenhas (eight overs for 28) and left-arm spinner Monty Panesar (six overs for 28) didn't bowl their full allocation of 10 overs each, a move that surprised Gayle.
"They've got roles in the middle of the innings," Collingwood explained. "Dimi and Monty probably don't have a role in the last 10 overs.
"But that's a learning curve for me. I'm not going to get every single decision right. I'm learning all the time as well."