The clubs had not met in the League for the past 49 years, but the win demonstrated that the U's have adapted well to their first ever season in the second tier.
The Essex club won this match on their first-half showing alone; they attacked from the outset and never gave Ipswich time to settle, and were duly rewarded with a ninth-minute goal.
Duguid's strike was to prove the only goal of the game although chances flowed at both ends all night.
Town goalkeeper Lewis Price should have perhaps done better with an initial effort from Jamie Cureton, which was struck from 20 yards out. Price could only parry the shot and Duguid was quickest to the loose ball to stab into the empty net.
It was a terrific moment for Duguid, who has been at Colchester his entire career, and the Layer Road faithful reacted with frenzied celebrations.
Ipswich continued to play second fiddle and the U's, inspired by a genuine captain's performance by Duguid and supreme displays from midfield duo Kemal Izzet and Kevin Watson, went in search of more goals before the break.
Cureton went close on a couple of occasions, but the hosts almost paid for their wasted chances in the 40th minute when Darren Currie's cross picked out Alan Lee. However, the Ipswich striker volleyed wide.
The Suffolk visitors showed a marked improvement in the second half and thought they had equalised in the 48th minute, when Jon Macken bundled home the loose ball after strike partner Lee had a shot blocked by Aidan Davison.
Town celebrated the leveller, only for referee Lee Probert to award a free-kick to the hosts for an alleged push on the goalkeeper.
The two keepers then made excellent saves. Price denied Chris Iwelumo with an instinctive block, before Davison prevented Ipswich substitute Billy Clarke equalising with an equally impressive save in the 72nd minute.
Ipswich stepped up a gear late on but could not find a way to beat Davison.