Although some of the Spireites - who reached the last four in 1997 - football was attractive, they never overcame a strong home defence.
Andy Crosby was the powerhouse and the silky skills of Ian Baraclough helped add weight to supporting the on-fire strikeforce of Paul Hayes and Steve Torpey.
Mark Allott tried valiantly to spark life from the visiting attack with little success, while at the back big men Steve Blatherwick and Ian Evatt were both commanding.
Scunthorpe made the early opening and Torpey got in an a header from Cliff Byrne's cross that was not too far off target and then the mountainous Blatherwick stepped in to halt Hayes following a mistake by Derek Niven.
The Spireites replied with Allott driving in a left-foot shot from the edge of the box which forced Paul Musselwhite to save at the foot of his left-hand post.
However, it was the Iron who broke the deadlock in the 13th minute.
Byrne knocked the ball into Torpey who fed Hayes and he took the ball in his stride to drive home a fine right-foot shot.
Shortly afterwards Richard Kell struck the ball over the top as the home side enjoyed quite a good spell, although it was the dangerous Allott who again threatened with a left-foot drive that was off target.
Caleb Folan then pushed the ball too far ahead and allowed Musselwhite to save easily.
Scunthorpe almost increased their lead after 49 minutes when Peter Beagrie swung in a corner and Crosby got in a powerful header which was headed off the line by Shane Nicholson.
Chesterfield's reply was a similar header from Blatherwick but if failed to trouble Musselwhite and then when substitute Tcham N'Toya-Zoa got away he blazed over the top.
United wrapped the game up with a second goal in the 76th minute.
Substitute Cleveland Taylor made space on the right and eventually crossed for Baraclough who collected the ball well before driving in a sweet left-foot shot that was worthy of winning any game.
