The Hampshire skipper, who scored a century and a half-century in England's 3-0 ODI series win over Pakistan, was simply impossible to bowl to as Hants chased down a stiff-looking target of 184 on a lovely's summer's evening at the Ageas Bowl.
Vince's 102 off 59 balls means Sussex still need a point - so either a tie or a win - at Kent on Sunday to make sure they finish in the top four and reach the last eight.
Remarkably it was Vince's second match-winning Blast knock of the day. This had been the second part of a double header for the hosts and his 63 set up an 18-run win over Essex - and that means Vince's side can still get in that top four themselves.
The Vince masterclass came after a good-sized crowd had been treated to some big hitting by the Sharks, led by skipper Luke Wright and Ravi Bopara, who scored 54 and 62 respectively.
Sussex won the toss and decided to bat first and Phil Salt, his tail up after making his England debut and helping them to an ODI series win over Pakistan, struck the first ball of the match for four only to be caught at backward point off the second, Brad Wheal showing a safe pair of hands off spinner Liam Dawson's bowling.
That set up a stand between two of the English T20 game's long-serving players, Wright and Bopara, and it was the skipper who got the Sharks innings moving with four fours in one over after a watchful start.
Bopara also started to warm to the task and overs by Scott Currie and Colin de Grandhomme earned Sussex 31 runs - forcing Hants to turn to pinners Mason Crane and D'Arcy Short to take the pace off the ball and the innings.
Bopara hit the first six of the innings - as straight as you like - off Crane in the ninth over and the runs started to flow nicely, with Wright reaching his 50 first and Sussex reaching 100 at the end of the 11th over. The pair totted up a 100 partnership in just 65 balls, Wright out soon after, caught by James Vince off Currie for a 40-ball 54 featuring nine fours.
Delray Rawlins and Bopara were soon picking up where they left off in a match-winning partnership at home to Essex last week, finding a gap between two fielders with a lovely reverse sweep off Crane. Bopara then passed 50, having faced 36 balls,
Rawlins hurried along to 22 off just ten deliveries but popped a catch up to Vince off Dawson, who had been a thorn in Sussex's side throughout his spell, which he ended with 2-15.
Bopara was eventually out for 62, off 42 with three sixes, and when David Wiese was superbly caught at the wide long-on boundary by Tom Prest, Sussex were just losing their way a little at 156-5. But Rashid Khan gave the Sharks late impetus with an unorthodox 26 at a strike rate of 200 and the innings closed on 183-6.
Currie was the main victim of Sussex's big hitting - his four overs costing 54, though he did take two wickets.
Hampshire's reply started at a rate of knots as James Vince went about making short work of the stiff target, racing to 30 by the time the fourth over was halfway through with a series of well-timed boundaries to all parts. D'Arcy Short followed in his footsteps with the first six of the reply as Ollie Robinson struggled to find his line.
Vince, only a few days after his masterful England ton, was in imperious form and even the introduction of spin in the form of Khan and Archie Lenham did little to slow the home side's charge. Vince's 50 came off 27 deliveries with ten fours.
Sussex simply had no answer as Hants passed 100 in the 10th over, with Robinson, Mitch Claydon and Rawlins all taking heavy punishment.
Skipper Wright used Will Beer as his eighth bowling option in the 13th over - and he got the breakthrough with his first ball, bowling Short for 35. But at this stage it felt like the damage had been done.
Prest was soon into his stride, keeping the scoreboard ticking over as Vince closed in on a ton but Prest was bowled - also by Beer, who must have felt he should have been used a little earlier - to keep Sussex's slim hopes of salvaging the game alive.
de Grandhomme kept up the Hants momentum alongside Vince until being run out by Bopara trying to go for a quick single that was never on.
Vince duly passed 100 off 56 balls as the target was neared. He had entertained the crowd with 14 fours and three sixes along the way - but was soon on his way for 102 after hitting his own wicket off Robinson. Inevitably Vince was given a standing ovation as he walked off.
Joe Weatherley calmed Hampshire nerves with a couple of boundaries as they were at least made to work for the win by the Sharks bowlers but they got over the line by six wickets and with four balls of the final over - leaving Sussex with a bit to do at Kent on Sunday to get to those knockout stages.