The narrative follows the exploits of Lady Susan, a beautiful and charming widow whose husband has recently died. Lady Susan is an excellent conversationalist who manipulates men into falling in love with her; they forget her socially unacceptable behavior and incorrigible flirtations after merely speaking with her. At the outset of the novella, Lady Susan has sold off her late husband’s family estate instead of giving it to his younger brother, Charles Vernon, as is custom. There are implications that she has done this to maintain her opulent lifestyle and to pay off some debts she has accrued. As a result, Susan must find other places to live. She takes great glee in her freedom resultant from her husband’s death, although she knows she must marry both herself and her daughter, Frederica, to continue her lifestyle.

A month after her husband’s death, Susan goes to visit the Manwarings for three months, which is where the audience finds her at the beginning of the novella. The Manwarings reside in Langford, and Susan admits that she has seduced the married Mr. Manwaring into falling in love with her right under the nose of his wife. It is unclear whether or not she actually commits adultery with him, as the sexual extent of their relationship is obfuscated by Susan’s own lies and manipulations. Mrs. Manwaring is utterly beside herself, and the familial chaos that ensues endlessly entertains Susan, although she realizes that she has worn out her welcome in their home. Susan also successfully convinces Sir James Martin to put aside Mr. Manwaring's sister for her own daughter, Frederica, even though both Susan and Frederica find Sir James obnoxious and weak. Susan admits to her confidante and co-conspirator, Mrs. Alicia Johnson, that Susan briefly considered the young Sir James as a possible matrimonial match for herself but has decided that his wealth alone will not make their marriage a happy one.

After fleeing Langford, Susan leaves Frederica at an expensive London school she cannot afford. She and Alicia deceive Mr. Johnson, Alicia’s husband, into allowing the two friends to spend time together whilst she is in London, during which time they hatch a plan to allow Susan to continue writing letters to Manwaring and encouraging his affection under the guise of Mrs. Johnson’s name. Shortly thereafter, Susan leaves London for an extended stay at her brother-in-law’s country house in Churchill at Charles’s behest, even though Susan does not like either Charles or his wife, Catherine. Susan decides to use this stay to figure out how to gain the most out of matrimonial plans for herself and her daughter.

Her stay at the Vernon’s is not without mischief itself, as Charles’s wife, Catherine, does not like Lady Susan, mostly because Susan had previously tried to prevent Charles from marrying Catherine altogether. Similarly, Catherine has also heard tales of Susan’s exploits with married and single men alike, tales that have also reached the ears of Catherine’s bachelor brother, Reginald. Catherine begs Reginald to visit to protect her from Susan’s behavior, and Reginald hastily agrees: He wants to see the infamously deceitful coquette for himself, astounded that any man could be so dumb and blind as to fall for Susan’s manipulations.

When Reginald visits, he too succumbs to Susan’s charms and ends up falling in love with her after Susan convinces him that all the rumors about her behavior are merely slander. Susan enjoys being able to easily manipulate Reginald, who is much younger than she, especially because it upsets his sister, Catherine. Susan also enjoys the challenge because she knows Reginald’s previous bias against her, making her victory over him all the sweeter. Upset at the fast and undeniably flirtatious friendship that has developed between Susan and Reginald, Catherine desires Reginald to return to their parents’ house away from Susan’s spell to care for their ageing father. Catherine becomes so upset that she requests her parents intercede and nip this relationship in the bud. However, even when Reginald’s father gets involved, Reginald argues that nothing is happening between himself and Susan, claiming that they are merely friends.

During this time, Susan corresponds with Alicia, whose husband does not approve of and eventually forbids their friendship. Susan relays her manipulations to Alicia, who takes great delight in living vicariously through Susan. Alicia tries to convince Susan to marry Reginald. However, Susan considers Reginald a worse catch than Mr. Manwaring, despite the pesky fact of Mr. Manwaring still being married. Susan continues to plan to marry Frederica off to the graceless and weak (albeit extremely wealthy) Sir James Martin, whom Frederica openly despises. After learning her mother’s continued machinations to marry her off to a man she despises, Frederica runs away from school and eventually comes to stay at Churchill.

Although Catherine initially laments that she will also have to deal with Susan’s daughter, Catherine finds Frederica entirely unlike her mother and therefore utterly charming. Catherine watches Frederica fall in love with Reginald, who by now only has eyes for Lady Susan, and Catherine deeply desires to see Reginald and Frederica wed if only to relieve her brother from the clutches of Lady Susan. In his typical gracelessly annoying fashion, Sir James Martin shows up uninvited, complicating Lady Susan’s—and Catherine’s—plots. Terrified of being married off to a man she despises, Frederica pleads with Reginald to intercede on her behalf after being prohibited from mentioning her feelings either to Charles or Catherine. Once Reginald hears of Lady Susan’s plots, he temporarily recognizes her for what she is and plans to leave Churchill at once for his familial home, to the extreme happiness of his parents and Catherine. However, Reginald speaks with Lady Susan, who convinces him that Frederica’s engagement to Sir James was a big misunderstanding, as she would never marry her daughter off to a man Frederica so openly loathes. This is a lie, but Susan’s artful arguments win over Reginald and deepen his affection for her, much to Catherine’s chagrin.

Believing she has successfully ensured her future, Lady Susan returns to London in an attempt to cement the marriage of Frederica to Sir James, only to find that Mr. Manwaring has followed her there as he has become obsessed with her. Blinded by infatuation, Reginald also follows Susan to London. Lady Susan tries to balance the two lovers, planning to marry Reginald without completely snubbing the still-married Manwaring. However, in her attempt to make sure their paths do not cross, she sends Reginald to Alicia Johnson’s house, where Mrs. Manwaring, who was Mr. Johnson’s ward, has come to plead with Mr. Johnson to do something about her husband’s infidelity and Lady Susan’s machinations. Reginald hears the entire story and is disgusted at Lady Susan’s actions, finally realizing her for what she is. Lady Susan attempts to rectify the situation albeit not very diligently; when she is unsuccessful, Susan writes Reginald off as an idiot. Reginald decides she is a coquette and realizes all the rumors about her are true, ending their relationship.

In the epilogue, Reginald flees from London to lick his wounds while Lady Susan still attempts to get Frederica to marry Sir James. However, an influenza outbreak necessitates Susan sending her daughter back to the Vernon’s house in Churchill. There, Catherine tries to get Reginald to agree to marry Frederica while Lady Susan ultimately marries Sir James. The anonymous narrator suggests that Susan will never be happy yet her daughter, Frederica, might get her wish and end up marrying Reginald.