The 77-year-old, affectionately known as 'Blowers', has worked on TMS since 1972.
His final match will be the Test between England and the West Indies at Lord's which starts on September 7.
"All good things come to an end," he said in a statement.
"After nearly 50 years in the Test Match Special commentary box, I have decided the time has come for the last of the old farts to hang up his microphone.
"In all honesty, at the age of almost 78, although I am still rather keener than mustard, I find it harder work than I once did. And I wouldn't want to let TMS down.
"You haven't heard my final 'My Dear Old Thing' quite yet. Happily, I shall be commentating next month on the first two Tests against South Africa, and then for the last one of the summer against the West Indies at Lord's.
"I leave, supremely confident that TMS is in the safest of hands, led by the ageless Aggers. In the end, I think he will come to be seen as the best of the lot.."
Blofeld is loved by many TMS listeners for his idiosyncratic approach to commentary.
He is as likely to make reference to pigeons, buses and the cakes on offer in the commentary box as he is to what is happening on the field of play.
His statement continued: "Listeners will now be relieved to know that their chances of being told the right name of the fielders at third man and fine leg have greatly increased.
"I hope some will be sad that they will now hear less about the lifestyles of pigeons, seagulls, and helicopters although I fear the general feeling will be one of huge relief.
"Now, I shall be able to come to the cricket without worrying about who is lurking down at third man. I shall also be able to have a drink without feeling I am being politically incorrect. And hallelujah to that!"