- "Downtown City. Home to two million people. Make that two million and two."
- —Blythe Baxter, Blythe's Big Adventure Part One
Downtown City is the main setting in the Littlest Pet Shop series and home to most characters. Blythe Baxter lived in her hometown until her father got a promotion in Blythe's Big Adventure Part One, which caused them to have to move into the city. Its layout seems to resemble that of New York City, specifically Manhattan Island.
- 72 Oak Street - Inhabitants: Blythe Baxter, Roger Baxter and Sunil and Vinnie's owners.
- Biskit Mansion - Inhabitants: Brittany and Whittany Biskit, Fisher Biskit, Eliza Biskit and François
- Alice's apartment building - Inhabitants: Alice and her mother.
In War of the Weirds, Vinnie suggested that the aliens could have decided to invade Uptown City, and Sunil suggested perhaps Midtown City because "they deserve it".