Billy Sharp took his goal tally for the season to 24 with two strikes to move Scunthorpe further clear at the top of League One.
Crewe scored first when Luke Varney converted Michael Higdon's cross after Joe Murphy had initially saved the goalscorer's shot.
Sharp volleyed in the equaliser from 10 yards before Jermaine Beckford scored with a superb individual effort.
And Sharp made the points secure when he headed home Matt Sparrow's cross.
Crewe: Williams, Woodards, Baudet, O'Donnell, Moss, Lowe, Cox, Roberts, Rix (Jack 75), Higdon, Varney.
Subs Not Used: Tomlinson, Pope, Carrington, Coo.
Booked: Varney.
Goals: Varney 26.
Scunthorpe: Murphy, Mulligan, Crosby, Foster, Ridley, Sparrow (MacKenzie 83), Hinds, Goodwin, Taylor, Sharp, Beckford (Williams 83).
Subs Not Used: Lillis, Butler, Hurst.
Booked: Hinds, Mulligan.
Goals: Sharp 29, Beckford 40, Sharp 62.
Att: 4,842.
Ref: R Olivier (W Midlands).