The Superchargers varied attack, led by Adil Rashid’s three for 13, prospered in sluggish conditions to restrict the Invincibles to 127 for six, including 27 off the last eight balls.
England leg-spinner Rashid was on a hat-trick as the Oval side slipped to 60 for six before Jason Roy’s unbeaten 52 off 43 balls ensured respectability.
But the Superchargers, on the back of two defeats and a washout, got home with three balls remaining thanks to Yorkshire star Brook and Simpson, who hit Tom Curran for four over backward point and six straight with 11 needed off the last five.
The Invincibles, who had not taken the field since an opening night win on July 22, struggled after opting to bat in this six-wicket defeat.
The extra pace of seamer Brydon Carse was particularly effective early on, and he struck once.
When Matty Potts bowled visiting captain Sam Billings for three, aiming an ugly carve through the off-side, Invincibles were 49 for four after 45.
Rashid’s first wicket was powerful South African Colin Ingram caught at deep cover - 44 for three after 39.
He then had Laurie Evans caught at deep midwicket and Jordan Clark brilliantly caught at slip by Dane Vilas, leaving the visitors six down with 42 balls remaining.
Opener Roy remained unbeaten while struggling for timing.
But that timing arrived during an imperative late unbroken seventh-wicket 67 partnership with Curran.
While Curran finished with 34 as they more than doubled the team total, Roy clattered the last three balls from David Willey for two sixes down the ground and a four.
Curran and Saqib Mahmood then removed Adam Lyth and Willey as the Superchargers reply fell to 23 for two after 21 balls.
As Mahmood stayed on to bowl 10 balls straight, Australian Chris Lynn pulled him for six and drove him for four on the way to 48 off 48.
But it was Brook who provided the impetus during a third-wicket partnership, and he faced 30 balls in all.
In taking the target from 75 off 50 balls to 32 off 25, he hoisted Tabraiz Shamsi for a straight six.
Lynn holed out to Sunil Narine’s spin and Vilas did likewise off Lancashire team-mate Mahmood - 98 for four and 30 needed off 18.
Brook found the cover boundary off Curran as the equation became 17 off 10 with Simpson now for company. And it was the latter who sent the 10,859 crowd home happy.
Superchargers opener Chris Lynn said: “Our first two games were probably the most entertaining in the tournament, but we were on the losing side. It was a bit heartbreaking.
“But we showed a lot of character to get the win.
“Today was more of a polished performance, and we executed our skills better.
“The wickets are a lot more low-scoring, and sometimes you have to put your ego aside and play the role the team needs.
“Our bowlers were very good. Rash and Mujeeb are world-class through the middle.
“It’s early doors in the tournament, and that washout point we got at Manchester may come into play.”