The contract expires at the end of the year and Robin Auld, sales and marketing director for Domino's, has followed up his comments from earlier this year that the sponsorship's effectiveness has "died away" by declining to extend it.
Auld today said: "Our sponsorship of 'The Simpsons' has been instrumental in our growth, especially so in the early days when 'The Simpsons' was our principle branding platform.
"It was a perfect affiliation and we are delighted with the results, helping us reach millions through what remains a TV institution. However, all good things must come to an end and we now feel its time to move on to new opportunities."
The Fox cartoon series is broadcast on Sky One every night and each episode is watched by around 400,000 people.
Domino's sponsored the second series of ITV1 show 'Britain's Got Talent' in spring this year, enjoying audiences well above 10m each week.
It adapted the content of its sponsorships in the wake of Ofcom introducing tighter rules on the advertising of food high in fat, salt or sugar two years ago. It switched from a focus on its products to a focus on services such as online pizza ordering.