Gary Hooper gave the Iron a dream start after just five minutes before a Paul Hayes penalty handed them a comfortable and deserved 2-0 lead at the break.
Matt Sparrow made it three just after the restart before Millwall rallied in impressive fashion to set up a nervy finish with goals from Neil Harris and Tony Craig.
The Iron started the encounter in determined fashion and Hooper put them in front early on, collecting a pin-point throughball from Hayes before firing neatly past David Forde from the edge of the penalty area.
Hayes netted a crucial second from the penalty spot after 16 minutes following Zak Whitbread's handball before Sparrow made it 3-0 from 12 yards after 51 minutes.
Half-time substitute Harris half-volleyed home to bring the Lions back into contention shortly after, before Craig prodded a goalmouth scramble into the net in the 69th minute to give Millwall hope, but Scunthorpe held on for the three points.