The 25-year-old Aucklander has registered scores of 78 not out, 91 not out, 85, 77, 70 and 51 across his last six international innings in all forms of the game.
Guptill was also dominant throughout Auckland's successful HRV Cup campaign this summer, hammering 504 runs at an average of 72.
Set 148 to win after South Africa posted an under-par 147-6, Guptill anchored the home side's run chase, while Kane Williamson chipped in with 24.
On a slow wicket that both sides failed to dominate the bowling on, Guptill plundered four sixes and five fours and built his man-of-the-match innings smartly.
Local lad James Franklin was afforded the honour of hitting the winning runs as he crunched a four through the covers to get New Zealand home with four balls to spare.
One big six Guptill struck clattered the roof of Westpac Stadium and brought back memories of a Craig McMillan maximum from years ago which cleared the roof but on the other side of the arena.
The knock was Guptill's fourth international Twenty20 50 and 13th across all teams in the shortest form of the game.
New Zealand bowled well after winning the toss and electing to take the ball, although Kiwi stand-in skipper Brendon McCullum may have wished he gave more overs to his spin bowlers.
Kyle Mills watched his four overs of medium pace disappear for 44 runs, while off-spinner Rob Nicol bowled one over for three runs and Ronnie Hira's two overs of left-arm orthodox only conceded 12 runs and picked up the vital wicket of AB de Villiers.
Nathan McCullum opened the bowling with his tweakers and set the tone for the home side as he claimed 1-16 from four overs and he combined with brother Brendon for the wicket of Colin Ingram as the younger of the Otago siblings stumped the South African No 3.
Tim Southee was impressive with the ball as the right-armer claimed 3-28 from four overs as he mixed up his pace and bounce to great effect, while Guptill's night began on a high as he was sharp in the field as he took a catch and ran out Hashim Amla.
Doug Bracewell also continued his fine summer, bowling three overs for only 10 runs.
The teams meet again in Hamilton tomorrow for the next Twenty20 encounter before heading to Auckland to wrap up this leg of the tour with the third 20-over match in Auckland.
They then turn their focus to the 50-over form for three games before they play as many test matches.
- Daniel Richardson
