Northants set a testing target of 187 to win in Derby, with Zaib hitting a T20 career-best 92, but the home side coasted home with six wickets and six balls to spare.
It was a below-par bowling performance from the Steelbacks, who suffered their first defeat in six games.
All the attack endured tough spells and struggled with their economy, with Freddie Heldreich emerging as the pick of the bunch with two for 33 from his four overs.
But Zaib insisted the defeat was more down to some exceptional batting from the home side, and in particular Madsen, rather than his own team's bowling.
The right-hander hammered 73 from just 37 balls, hitting 10 fours and two sixes, while skipper Masood led from the front with 57 from 43.
The pair put on 95 in a punishing and match-winning third wicket stand in just 9.2 overs, and despite a couple of late wickets, the Steelbacks couldn't claw things back.
"It's a shame we couldn't get over the line but they batted very well, especially in that middle period," said Zaib.
"Wayne Madsen is hard to bowl to, he can hit 360 degrees, and I felt for the bowlers tonight to be honest.
"But he has done that to many teams."
The fact the Steelbacks had a target to bowl to was chiefly down to Zaib, who was run out in the final over having made a superb 92 from 58 balls, hitting eight fours and four sixes.
It was a crucial knock as the team's main men in the tournament so far, Chris Lynn and Josh Cobb, were both dismissed in the opening six-over powerplay, along with Ben Curran.
Zaib held things together as the Steelbacks recovered from 34 for three to post 186 for seven, with Jimmy Neesham hitting 28 from 20 balls.
"I thought we did quite well getting that total," admitted Zaib, who has now twice scored half-centuries in this season's Blast.
"But they know their ground and batted very, very well and sort of killed the game in that middle period."
It was a fifth straight win for the Falcons, who leapfrogged the Steelbacks to go second in the North Group table, with Northants dropping to third.
Both teams trail leaders Lancashire Lightning by one point, having played a game more.
Falcons skipper Masood was delighted with the win, and said: "We finished the powerplay off strongly and then Wayne Madsen played an incredible knock, he made my job easier.
"I didn't have to do anything silly or extraordinary, I just had to make sure I was at the other end, get the odd boundary away and give him support and the strike.
"He just literally put them under the pump and by the 10th and 11th over we were down to chasing eight or seven an over with eight wickets to go which is always ideal.
"I think in terms of the chase we never put ourselves under pressure and that was close to a very perfect performance chasing.
"We are lucky Wayne Madsen has played his cricket for Derbyshire and given his heart and soul for Derbyshire and no matter what I say about him it can never be enough."
The Steelbacks will be hoping to get back to winning ways when they host Birmingham Bears at the County Ground on Wednesday night (start 6.30pm).