Our Miss Brooks was a hit on radio from the outset; within eight months of its launch as a regular series, the show landed several honors, including four for Eve Arden, who won polls in four individual publications of the time. Arden had actually been the third choice to play the title role. Harry Ackerman, at the time CBS's West Coast director of programming, wanted Shirley Booth for the part, but as he told historian Gerald Nachman many years later, he realized Booth was too focused on the underpaid downside of public school teaching at the time to have fun with the role. Lucille Ball was believed to be the next choice, but she was already committed to My Favorite Husband and didn't audition.

Produced by Larry Berns and written by director Al Lewis, Our Miss Brooks premiered on CBS on July 19, 1948. According to radio critic John Crosby, her lines were very "feline" in dialogue scenes with principal Conklin and would-be boyfriend Boynton, with sharp, witty comebacks. The interplay between the cast - blustery Conklin, nebbishy Denton, accommodating Harriet, absentminded Mrs. Davis, clueless Boynton, scheming Miss Enright - also received positive reviews.

Arden won a radio listeners' poll by Radio Mirror magazine as the top ranking comedienne of 1948-1949, receiving her award at the end of an Our Miss Brooks broadcast that March. "I'm certainly going to try in the coming months to merit the honor you've bestowed upon me, because I understand that if I win this [award] two years in a row, I get to keep Mr. Boynton," she joked. But she was also a hit with the critics; a winter 1949 poll of newspaper and magazine radio editors taken by Motion Picture Daily named her the year's best radio comedienne.

For its entire radio life, the show was sponsored by Colgate-Palmolive-Peet, promoting Palmolive soap, Lustre Creme shampoo, and Toni hair care products. The radio series continued until 1957, a year after its television life ended.