The 46-year-old will appear in the Sherlock Holmes drama's seventh episode, TVLine reports.
Edelstein will play Heather Vanowen, the CEO of a PR firm who meets Sherlock (Jonny Lee Miller) when her company is targeted in a bombing.
Best known for her role as Dr. Lisa Cuddy on House, Edelstein has also appeared on The Good Wife and The West Wing.
Callie Thorne - who currently stars in USA series Necessary Roughness - has also been cast on Elementary. Debuting in the show's sixth episode, her character Terry D'Amico is an NYPD detective who shares a past with Sherlock's ally Captain Gregson (Aidan Quinn).
Thorne's additional credits include roles on Rescue Me, Burn Notice, Prison Break and The Wire.
Elementary debuted last Thursday (September 27) on CBS in the US, attracting 13.4m viewers. The series will air in the UK on Sky Living from later this month.
> Elementary pilot recap: Is the US Sherlock reimagining any good?
> Elementary star Lucy Liu: 'Sherlock creators like our show now'
Watch a clip from Elementary below: