Harley Quinn forsøger at klare sig på egen hånd i Gotham City. Hun får hjælp af Poison Ivy og en broget skare af vragede DC-skikkelser og forsøger at sikre sig en plads blandt den største samling af skurke: Legion of Doom!

Harley er fast besluttet på at blive optaget i Legion of Doom og prøver at blive bemærket ved at blande sig i et af deres kriminelle foretagender med hjælp fra sin slyngveninde, Poison Ivy. Lykkes det hende, eller opnår hun blot ydmygelse?

Realizing she needs a crew to pull off heists that will attract the Legion of Doom’s attention, Harley attempts to recruit Dr. Psycho and Clayface.

In search of a nemesis, Harley goes after Batman, but ends up with an adolescent Robin, making her the laughing stock of the criminal underworld.

When Harley suffers a paralyzing identity crisis, her crew must enter Harley’s mind to free her with the help of Dr. Psycho’s telepathic powers.

When Clayface loses his arm in a heist, it turns out to be not only evidence for Jim Gordon, but also a key witness against Harley and her crew.

Harley recruits her friend and mentor Queen of Fables to help her steal a force field from STAR Labs, to steal a weather-changing machine, so she can impress the Legion of Doom. Meanwhile, Poison Ivy dates Kite Man.

Harley gets an invite to the Legion of Doom’s prospective members party, but Ivy discovers that it’s Lex Luthor they’re really after.

Now a member of the Legion of Doom and The Joker’s equal, Harley finds herself spending time with him. Will she slip into her old ways?

Harley must rescue Ivy from the clutches of Scarecrow, who’s trying to harvest her pheromones to make a super toxin that turns plants into sentient monsters.

Harley thinks the Legion of Doom is behind Ivy's capture and the tree monsters currently ravaging Gotham. But it's a trap!

In the season finale, Harley has her final showdown with the Joker, when [spoilers] [spoil] [spoilers]. Will they [spoiler]? Maybe. But you can bet they [spoiler]!