Carlisle crashed out of the FA Cup after a lightening strike by Scunthorpe's Martin Carruthers gave the visitors a 1-0 win.
Carruthers' 25 minute winner also earned the Iron the prize of a lucrative third round home tie with Premiership Leeds.
After Carlisle's Mark Summerbell was sent-off for two yellow cards, ten-men United battled on bravely, peppering the Scunthorpe goal without finding the equaliser.
Scunthorpe's goal on 25 minutes followed Summerbell's first foul, Ian Kilford took a quick free-kick that found Carruthers who stabbed a shot across home keeper Matty Glennon and into the net.
On 27 minutes Carlisle's Peter Murphy hit a 40-yard pile driver that struck the upright, and then on 54 he blasted a free-kick from the edge of the box into the defensive wall.
Murphy also came close again for the Cumbrian club on 67 minutes, this time with another shot which whistled just wide of the post.
Carlisle's best chance came on 75 minutes when Scunthorpe keeper Tom Evans had to be at full stretch to collect a fierce shot from Richie Foran as the home side pressed.
But the visitors held firm to earn their place into the next round of the competition and seal a clash with Terry Venables' Leeds.