At the beginning of Lady Friday, a cleaner tells Leaf that everybody has become infatuated with a "Dr. Friday", because she is so beautiful and refined; as a result, every member of the staff calls her Lady Friday. Lady Friday, a Denizen and Trustee of the House, is in command of the Middle House.
It is later revealed that Lady Friday has kidnapped thousands of people and taken them to Avraxyn, the world that is mentioned in Sir Thursday as the world from which the Skinless Boy's mind-controlling mould originated. There, Lady Friday drains from them their emotions and memories, which she then drinks in order to experience them (being a House Denizen herself, she cannot have these emotions herself, but must take them from others).
Arthur, the Piper, and Superior Saturday all receive messages from Lady Friday, saying she has abdicated the rule of the Middle House and that the first of the three who can reach her Scriptorium in the Middle House can claim the Fifth Key and her domain as their own. Along with each message is sent a Transfer Plate that sends whoever touches it straight to the Middle House (which is a giant, terraced mountain). Arthur accidentally takes the plate and is sent to the Middle House; he still retains the Fourth Key.
While the Piper is contemplating what to do with his Plate, the Piper's Children Suzy Turquoise Blue and Fred Initial Numbers Gold, along with their loyal New Nithling bodyguard Ugham, grab it and are transferred to the Middle House. In the Middle House, Arthur takes refuge in a Manuscript-Gilding workshop, where he fights off some Fetchers and eventually meets Fred and Suzy. At first, he does not trust them, fearing their allegiance to the Piper; however, they and his own inclinations convince him that they can be trusted. Around their necks are bindings that bend them to the Piper's will; these are removed by Arthur with the power of the Fourth Key, at Suzy's behest.
While on the way to the Scriptorium, they meet some of the Middle House's Winged Servants of the Night, who are fighting several of Saturday's elite forces, known as Artful Loungers. Arthur singlehandedly defeats four of the latter, earning the friendship of the Servants. While flying to the pinnacle of the mountain, on which stands the Scriptorium, Arthur is guided to the Fifth Part of the Will, which is chained within the lair of the Winged Servants. This part of the Will (shown on the British cover), a bizarre creature having the head of a fox, the upper torso of a bat, the lower body of a blue dragon, and four legs, is much more likable than the other parts; it is stated that this part, presumed to embody the virtue of moderation, is the part without which the Will has no self-control.
When Arthur reaches the Scriptorium, he finds that the Piper has apparently killed Saturday's Dusk. The Piper orders Ugham to pick up what is supposed to be the Fifth Key; when Ugham does so, a trap from Lady Friday, in the form of an entrance to the Void of Nothing, is sprung. Ugham is instantly dissolved; as the breach gets bigger, Arthur decides to use the Fourth Key, even if it turns him into a Denizen, to close the hole. One Key alone is not sufficient to accomplish this task; therefore the Will advises him to call upon the power of the remaining Keys in his possession; the Keys appear with him, and he fixes the breach. To return to the Lower House, Arthur uses the Improbable Stair, the Architect's own personal transport, to transport himself, Suzy, and Fred to Monday's Dayroom. There, the butler Sneezer uses the Seven Dials to transport Suzy, Fred, Arthur, and their friend Dr. Scamandros to Friday's hideout.
They find that Friday has lost her self-control and is about to "experience" thousands of people at once. Arthur arrives just as Friday transfers their beings into the Key; having obtained mastery of the Middle House, he returns their experiences. He finds that his friend Leaf was among the people, but that his own mother is not. It is confirmed thereafter that Arthur's mother is not in the Secondary Realms, and is therefore deduced to be in the Upper House. Arthur gives all the keys to the Will, except for the Fifth, and decides to go to Earth to settle matters there before going after Saturday. As the book closes, Suzy gives Arthur a note that Ugham gave her before he died. It appears to be a piece of a letter sent from Sunday to Saturday or vice versa. It reads "For the last time, I do not wish to intervene. Manage affairs in the House as you wish. It will make little difference in the end. S". The sender of this message, 'S', is presumed to be either Saturday or Sunday and is later revealed to be Sunday in Superior Saturday.
- The final sentence may remind readers of the suggestion raised in Sir Thursday by Dame Primus that the Trustees are wittingly or unwittingly part of a plan to destroy the House, and itself makes the suggestion that the sender believes the House to be doomed.