The Whitney Cummings vehicle, which will premiere in September, focuses on the relationship between a happily unmarried couple.
Kaczmarek has now signed up to play Whitney's mother, Deadline reports.
The character, who has been married several times, is described as "outspoken".
The role was originally played by Beverly D'Angelo in the pilot, so some scenes are expected to be reshot with Kaczmarek.
Kaczmarek is possibly best known for her role as Lois in Malcolm In The Middle. Her other credits include Hill Street Blues, Cybill, Party Of Five, Raising The Bar and a recent guest appearance in Wilfred.
Cummings has recently defended the decision to use the multi-camera format and a live studio audience on Whitney.
The show will premiere on September 22 on NBC.
Watch a preview of Whitney below: