Hampshire 178 for 4 (Weatherley 59*, Vince 50) beat Somerset 173 for 6 (Smeed 52, Kohler-Cadmore 43) by five runs
Nathan Ellis produced two stunning death overs to condemn Somerset to their first defeat of this season's Vitality Blast as Hampshire Hawks made it four wins on the bounce.
But Australian quick Ellis went for three and four in the 17th and 19th overs to return one for 26, with Scott Currie defending 18 in the final over as Hampshire won by five runs.
Hampshire had only failed to defend 178 at the Ageas Bowl once before in T20s but Tom Banton and Smeed were desperate to add to the Zak Crawley-inspired Kent eight-wicket destruction in 2020. The duo piled on 69 runs in the powerplay with inventiveness, power and clean ball striking.
But Liam Dawson found a top edge out of Banton - who scored 31 in 21 balls - in the seventh over, only for his replacement Tom Kohler-Cadmore to blast Currie for three fours.
Smeed had returned a modest 70 runs in his first six innings of the summer but dominated with seven fours and a pair of sixes in a 30-ball fifty. But he fell two balls later when slogging Mason Crane to deep mid-wicket.
Sean Dickson lost his leg stump to John Turner, although Kohler-Cadmore heated up a lull with two huge sixes off Crane in the 16th over. But fell to a well-aimed Turner bouncer with 26 needed off 15 balls.
Aneurin Donald pulled off a stunning catch to send away Tom Lammonby as Ellis' 19th over only went for four to leave 19 required off the final Currie over.
Lewis Gregory was run out and despite still going for 13, Currie and the Hawks came out victors to end Somerset's six-game winning run.
Having been invited to bat first, Ben McDermott pulled, cut and ramped a trio of boundaries but fell in the third over to Matt Henry.
After his run of half-centuries was ended by Middlesex on Tuesday, Vince added Somerset to his victims this season, although with slightly less fluency than some of his imposing knocks earlier in the Blast.
Three fours brought up 54 for one in the powerplay, with two more sixes to follow in his 37-ball fifty - although after hitting Roelof van der Merwe back over his head for his second maximum he failed to strike a boundary off his last 14 deliveries before holing out to long-on.
Toby Albert had joined him in a 60 stand before falling to a swing to long on as Somerset took control of the middle overs thanks to Lewis Gregory, Ben Green and van der Merwe's squeezing.
Weatherley escaped the press firstly by carving van der Merwe twice to the cover boundary before upping the ante with two swats for six to take him to a 31-ball half-century.
Ross Whiteley had run hard to help in a 73-run stand, although he only personally managed a scratchy 14 off 15 balls. Whiteley was brilliantly caught by Smeed on the boundary before Donald's looping six over extra cover took the hosts to 178 for 4.