Matt Parkinson, who was released from England duty in order to feature on Finals Day, may have claimed four for 26, but it was Ben McDermott's 62 off 36 balls which powered Hampshire to 152 for eight.
Earlier in the day, Lancashire became the first team to chase down a 200-plus total on Finals Day as they overcame Yorkshire in the semi-final. However, they were unable to replicate that performance against Hampshire as they lost by a solitary run.
The finale was an extraordinary one as Lancashire required four runs from the final delivery of a thrilling match. Nathan Ellis' yorker cannoned into Richard Gleeson's stumps, but as fireworks lit up the night sky, replays showed the Aussie overstepped.
Ellis regained composure following the no-ball as Gleeson swung at fresh air with the free hit. The player scurried for a single, which ultimately wasn't enough to prevent Hampshire from claiming their third title.
The county have now equalled Leicestershire's record for the most domestic T20 titles in England.
Hampshire fast bowler Nathan Ellis told the BBC: "It was my own fault but I guess it added to the occasion. My heart sank when I saw the umpire's arm had gone up and I realised we were now in danger of losing the game.
"The scenario had changed. It meant that, if they now scored two, they would tie the game and win on losing fewer wickets.
"But James Vince was really good in the situation, He's definitely one of the calmer captains I've played under.
"He got us all together, made us take a few deep breaths, made sure everyone was aware of the situation - and that went a long way to helping us calm down and get our heads right again."
Skipper James Vince added: "The way Nathan Ellis regrouped was outstanding. He felt himself confident enough to go to that slower ball, and a lot of credit has to go to him.
"I just wanted to double check with the umpires what the situation was if it was a tie and that they would now win if they got two runs. But, when Nelly bowled his slow ball and we broke the stumps then we are able to celebrate for a second time.
"We have a never-say-die attitude in that team. We never feel like we're beaten. Our bowling attack has been top drawer throughout the competition. We've taken wickets at the right times.
"After the first four games we've been immense. And the final was just a great game of cricket."