For long periods Scunthorpe looked unhappy at the back after conceding an early goal and they have to thank striker Billy Sharp for a major contribution of two goals and the experience of Peter Beagrie to get them through the game.
Rotherham's Colin Murdock was a key figure for the opening 45 minutes before being replaced at the break with a groin strain.
John Mullin also excelled while loan man Barry Conlon worked hard up front.
Rotherham had a bonus start, going ahead after only three minutes following a foul by Andy Keogh on Murdock.
Grant Leadbitter's free-kick was floated high into the box and Martin Butler deflected the ball past Paul Musselwhite with his head.
That was a real shock and it took a shaky Scunthorpe rearguard some time to regain their composure.
Yet at the same time they forced Gary Montgomery into several good stops, particularly from teenager Sharp.
Rotherham almost grabbed a second goal in the 18th minute when Conlon and Michael Keane combined to set up Mullin but his header flashed wide.
Two minutes later Scunthorpe were level. It was veteran Beagrie who fired in a good cross and Sharp met the ball well for his ninth goal of the season.
That lasted just nine minutes though as Scunthorpe's defence had remained hesitant and they were caught out when Paul McLaren was not closed down and he turned well to crash home a fine left-foot shot.
Scunthorpe picked up the pace towards the end with Beagrie forcing a good stop from Montgomery.
The home side continued to press after the restart as the game maintained a hectic pace and Rotherham lost the plot on the hour.
A clash between Beagrie and McLaren resulted in the Millers midfielder being shown a straight red card by referee Martin Atkinson for lashing out.
And within a minute Scunthorpe made the extra man count when Beagrie's cross was cushioned by Keogh into the path of Sharp and he curled the ball inside the right-hand post.
The young Scunthorpe striker almost completed a hat-trick when set up by Peter Till but his late effort was just off target.