Playing at the ground where they were knocked out of the competition last season, the Cobblers fell behind to a fluke goal from Emmanuel-Thomas but showed good composure to battle their way back against Championship opposition.
Ben Tozer levelled things up 6 minutes before the break before Paul Turnbull scored what proved to be the winner on 54 minutes.
Another famous win for Northampton despite Ipswich fielding a much-changed side from their league opener and one that opens up the possibility of a Premier League side coming to Sixfields in the next round.
"The victory was fully deserved and that makes it even sweeter," boss Gary Johnson said on the club's official website afterwards.
"I did say to the players before the game that if they showed commitment I felt our football would come and some of our combination play outside the area was very good."