The children's show, which first premiered on Nov. 10, 1969, will mark the anniversary by airing an episode featuring first lady Michelle Obama for the season's opener.
She follows in a long line of first ladies to mingle with muppets. Barbara Bush, Hillary Rodham Clinton and Laura Bush have all had hosting honors.
The decades-old show has been thoroughly examined -- academic researchers have compiled more than 1,000 studies, making Sesame Street the most researched TV show in history.
Among them, one that suggests teens who watched the show have higher grades and spent more time reading for pleasure than those who missed it.
Sesame Street is currently midway through production of its 41st season.