Gary Roberts and a Sam Clucas brace in the first half were followed by strikes from Dan Gardner, Jimmy Ryan and a Roberts penalty as Chesterfield celebrated their biggest league win of the season.
Chesterfield went ahead in the sixth minute when Drew Talbot crossed from the left and Roberts was unmarked to smash the ball home from 12 yards.
Colchester’s hopes were dealt a double blow with two goals from Clucas in the space of a minute with the striker firing a Gardner cross in from 10 yards in the 16th minute and then racing clear to chip Chris Lewington.
The visitors still had chances and Tommy Lee made two more good saves to first deny Alex Gilbey in the 34th minute and then Chris Porter seven minutes later.
Only a goal-line clearance by Tom Eastman denied Gardner but his 20-yard shot went through the hands of Lewington in the 59th minute and Gardner sent Ryan in for the fifth two minutes later.
Roberts blasted in an 85th-minute penalty after he was tripped by Lewington to complete the rout.