Paul Hayes helped maintain Scunthorpe's 100% home record, firing home a second half winner against 10-man Preston.
The Irons went ahead when Andy Crosby headed home from Kevan Hurst's corner, but Preston equalised when Youl Mawene responded with a header of his own.
Scunthorpe regained the lead when Hayes shot under Andy Lonergan following Martin Paterson's neat backheel.
Preston missed the chance to level when Nicholls missed from the spot, while Andy Carroll saw red for retaliation.
Scunthorpe boss Nigel Adkins
"It was a super game, high tempo, loads of goalmouth action and thoroughly enjoyable.
"We're on 10 points now in the Championship after six games. It's a fantastic start for us.
"On any one given day, anybody can beat anybody. And that's what our philosophy is."
Preston manager Paul Simpson
"I think we deserved something. We created good opportunities, but if you don't finish your chances, you get punished.
"It's disappointing the way we conceded both goals, but I think there was a lot of good football tonight."
Of Andy Carroll's red card, he said: "I do think Andy Carroll reacted to something their player did to him."
Scunthorpe: Murphy, Byrne, Crosby, Butler, Youga, Sparrow, Goodwin, Baraclough (Taylor 89), Hurst, Hayes (Forte 73), Paterson (Iriekpen 89).
Subs Not Used: Lillis, Cork.
Goals: Crosby 24, Hayes 49.
Preston: Lonergan, Jones, Mawene, Chilvers, Davidson, Sedgwick (Whaley 81), Nicholls, Carter, Gallagher (Pugh 87), Agyemang (Ormerod 70), Carroll.
Subs Not Used: Chris Neal, Hill.
Sent Off: Carroll (62).
Goals: Mawene 44.
Ref: Richard Beeby (Northamptonshire).