The former Watford boss took over at the Sixfields Stadium in November 2011 but the board have relieved him of his duties.
"Aidy Boothroyd has left Northampton Town Football Club," read a statement on the club's official website.
"The decision was made by chairman David Cardoza after Saturday's loss to Wycombe Wanderers.
"The club will make no further comment at this time, but will provide a further update on Monday."
Former Gillingham manager Martin Allen has emerged as the early favourite to take over from Boothroyd - he was sacked by the Kent side in October.