Sesamstraat is the titular street where the central characters live on Sesamstraat. Sesame Street was designed to resemble an typical, inner city landscape, recognizable to children although slightly idealized. While many of the inserts were taken from its original show Sesame Street and took place in puppet-scale interiors (ranging from Ernie and Bert's Apartment and Charlie's Restaurant to the countless walls or the varying game show sets of Guy Smiley), the main storyline scenes have always focused or at least begun on the street and its environs, outside of special location episodes. It serves as a meeting place for human and Muppet cast members alike.

At the beginning the most central location was Piet's Workplace, the place where they all came to let things fixed. The next significant structure is the building which houses Sien's Store, a living room and basement where Tommie lived and invented stuff. Pino's nest was located on top of the workplace.

In the 1980s, the most central location was Sien's Store, the shop whose front stoops are a frequent gathering place for the main characters, and the home to Sien. The next significant structure is the building which houses the living room, Aart's living room and a bedroom for Tommie and Ieniemienie.

Between the two is a more open street area, a kiosk, highlighted by an old playground decorated with an old Renault for the kids to play in, later also a caravan where Frank lived. Next to it all was the place where Pino's nest was located.

From the mid 1980s through the late 1990s, the neighborhood expanded. Sien's store and the other locations were designed to be more changeable, so they could change the locations easier to create all kind of situations and rooms. The human characters and Muppets didn't live at one clear location, but interacted with all the others who lived there. For instance Tommie and Ieniemienie lived with Sien at first, but now they had their home with all the other characters. Even Pino's nest wasn't his only home anymore. This plot was created to show the diverse relationships you could have as a family.

In 2005 the set was changed radically. They abandoned the idea of a street and abstract ideas dominated the design. Sien's Store, Pino's nest and all the living rooms disappeared from the stage. Now they use square blocks for them and the trees transformed into giant broccoli. The place where the stories are read is now taped on a dune with a lighthouse.

The actual studio sets used for Sesamstraat have changed over the years, but for most of the recent seasons, the show has been taped at Studiocentrum in Mediapark Hilversum, utilizing stage 1 and 2.