The casting news came Monday, shortly after Abdul announced she would not return as a judge on "American Idol" next season.
Johnston is best known for her work on TV's "3rd Rock from the Sun" and "ER," as well as the films "Music & Lyrics" and "Bride Wars."
Usmagazine.com said Johnston will begin playing quirky office temp Helen in "Ugly Betty's" Oct. 9 Season 4 premiere.
Entertainment Weekly said Abdul was replaced because her list of demands were considered unreasonable.
"I've always considered myself a poor man's Paula Abdul," Johnston told EW.