Sussex were firm favourites to win their third game in a row when they needed 24 off four overs chasing a target of 148. Even when they lost in-form opener Chris Nash for 69 they were still in control with five needed off the final over.
Seamer Helm, though, kept his nerve. Jofra Archer played and missed at his first two balls before he skied the third to backward point where Steven Finn took the catch. David Wiese missed the fourth delivery, took two off the fifth but failed to make contact with the final ball to leave Middlesex celebrating an unlikely triumph.
Nash made 69 from 52 balls, his third successive half-century in the competition, with nine boundaries and had he been there at the finish Sussex would surely have won, but leg-spinner Nathan Sowter trapped him lbw in the 18th over before Helm took centre stage.
There was assistance for the bowlers throughout on a slow pitch. Steven Finn dismissed Sussex’s two danger men Luke Wright (6) and Ross Taylor (3) cheaply, but Nash seemed to have swung momentum back his side’s way when he struck three boundaries off Finn’s final over. Middlesex, though, kept chipping away while only Stiaan van Zyl (34) offered Nash the support he needed.
Mark Davis, Sussex coach, said: "It is very disappointing because we played really strong cricket for four-fifths of that game and were on top. We weren't smart enough with the bat, with the exception of Chris Nash who played really well again.
"On pitches like that which was slow with the ball stopping in the wicket you have to get bat on ball. If we'd done that we would have cruised to victory. We've still got a chance of getting into the top four but we probably need to win our last three, starting against Gloucestershire tomorrow."
Earlier, Middlesex had been indebted to a maiden T20 half-century from Steve Eskanazi in only his third game in the format as they finished on 147 for 6 after being put in. He came in during the fifth over after Chris Jordan had ended an opening stand of 30 between Paul Stirling and John Simpson when Simpson (9) drove a slower ball to mid-off.
Middlesex looked on course for a more competitive score when Eskanazi and Stirling were adding 40 from 29 balls for the second wicket. Stirling, returning to the side after injury, struck four boundaries and pulled George Garton over mid-wicket for six and was well set on 40 when he failed to clear long on attempting to drive left-arm spinner Danny Briggs over the top.
Briggs took another important wicket in the 12th over when he had England one-day captain Eoin Morgan (10) held by Wiese, who ran in from the mid-wicket boundary to take a superbly-judged diving catch. The South African only just avoided a head-on collision with Nash, who had to go off for treatment to a cut knee suffered as he took evasive action.
Eskanazi finished with 57 from 44 balls with five fours but Middlesex contained by some accurate Sussex bowling on a slow pitch which offered some seam movement. Sussex are only a point off the top four but need to beat Gloucestershire on Friday to keep their quarter-final hopes alive.