A goal in each half from Gary Hooper set Scunthorpe on their way to a third successive home win.
Hooper beat goalkeeper Mark Cousins before slotting home in the 36th minute then raced clear from halfway to drive in his 29th goal of the season.
Henri Lansbury, on-loan from Arsenal, then worked himself an opening before producing a bottom-corner finish.
Colchester's best chance came when Karl Hawley's rifled shot flew past keeper Joe Murphy but hit both bar and post.
Scunthorpe: Murphy, Wright, Mirfin, Pearce, Williams, Lansbury (Woolford 76), Sparrow, Trotter, Hurst (Togwell 59), Hayes, Hooper (May 83). Subs Not Used: Slocombe, Crosby.
Goals: Hooper 36, 59, Lansbury 69.
Colchester:
Cousins, Maybury, Trotman, Baldwin, Tierney, Perkins (Gobern 67), Hammond, Izzet (Jackson 68), Yeates, Platt, Hawley, Jackson (Hackney 71). Subs Not Used: Gerken, White.
Booked: Yeates.
Att: 4,304
Ref: Graham Scott (Devon).
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