The 64-year-old will appear in 7 of the show's initial 13 episodes, according to Deadline.
Larroquette - known for roles on Boston Legal and his sitcom The John Larroquette Show - will play Dwight Haverstock, a US senator with a dark past.
The actor won Emmys for his performances on Night Court and The Practice, while his recent credits include guest stints on CSI: NY and Chuck.
Infamous stars Meagan Good as a detective who returns to her hometown undercover to investigate the death of her former best friend, socialite Vivian Bowers.
Victor Garber, Tate Donovan, Gossip Girl's Ella Rae Peck and Katherine LaNasa will also star in the series, while True Blood's Wes Brown recently played Upstairs Downstairs star Neil Jackson on the drama.
> Two and a Half Men star Marin Hinkle joins NBC's Infamous
> Breakout Kings star Laz Alonso joins NBC's Infamous
Watch a clip from Infamous below: