The former Watford boss had been in charge of the Cobblers since November 2011 and his struggling side had picked up two wins and two draws from their last five games heading into the clash with the Chairboys.
But Wycombe's comprehensive victory at Sixfields was to be Boothroyd's last in charge with the club's Twitter account announcing his departure at 5:39pm.
"The decision was made by Chairman David Cardoza after Saturday's loss to Wycombe Wanderers," a brief statement added.
"The club will make no further comment at this time, but will provide a further update on Monday."
- Sports & Recreation
- Wycombe Wanderers