Possessed of a fine singing voice in his younger days, it was supposedly Frawley, not Al Jolson, who introduced the song "My Mammy" to vaudeville audiences. He was also an early and persistent exponent of the hit song "Carolina in the Morning". His film credits include Miracle on 34th Street, in which he portrayed "Charlie", the judge's campaign manager.

On I Love Lucy (1951), Frawley played Lucy and Ricky Ricardo's landlord Fred Mertz. He and Vivian Vance, who played his wife Ethel in the series, despised each other.

On one occasion, he derided Vance for trying to tell him how to do a simple soft-shoe number, declaring that "I've been in vaudeville since I was five years old", and would "probably end up teaching old fat-ass (Vance) how to do the fucking thing!"

The two co-stars were given the opportunity to move into their own "Fred and Ethel" spin-off once Lucy had run its course in 1959. Despite his animosity towards her, Frawley saw a lucrative opportunity and was quite game, but Ms. Vance nixed the idea, having no interest in ever working with Frawley again.

Even time would not dull their mutual hatred; Vivian Vance once told Ralph Hart, who played her son on The Lucy Show, "You're much cuter than that old poop." Frawley, when asked on the set of his show My Three Sons about his former co-star, Frawley shamelessly answered his questioner with the words: "That miserable cunt!"

Frawley next hit it big on My Three Sons in his role as "Bub". He reportedly never felt comfortable with the out-of-sequence filming method used on My Three Sons after doing I Love Lucy in sequence for years. (Most television series are filmed out of sequence, but My Three Sons was unusually so: each season's episodes were arranged so that series star Fred MacMurray could shoot all of his scenes during a single intensive two-week period; Frawley and the other actors worked around the absent MacMurray the rest of the year.)

By almost all accounts, Frawley's off-screen personality was not all that much different from his on-screen one. A notorious misanthrope, with one brief failed marriage behind him and a fondness for the bottle, he lived in the same spare bachelor apartment for most of his years in Hollywood.

According to Desi Arnaz's memoir A Book, Frawley eventually lost his driver's license due to drunk driving, and befriended a cabbie who drove him around regularly.

When deciding whether to hire Frawley for the role of Fred Mertz on I Love Lucy, Arnaz made it clear to him that, if he showed up drunk for work, Arnaz would "work around it" twice, but after that, Frawley would not only be fired from the program but blacklisted throughout the entertainment industry. Frawley, whom no one would hire at that point, readily agreed.

He never showed up drunk on the set at all, and, in fact, Arnaz became one of his few close friends.

Poor health forced Frawley's retirement. He was dropped from My Three Sons after the studio could no longer obtain insurance on him. He was angry about being let go, and developed a dislike of actor William Demarest who replaced him, accusing him of stealing his job. (One of his final performances was an October 1965 guest appearance in Ball's subsequent series The Lucy Show.)

He collapsed of a heart attack on March 3, 1966, and died, aged 79. He had been walking along Hollywood Boulevard after seeing a movie.

After he died, Arnaz took out a full-page ad in the trade papers, consisting of Frawley's picture, edged in black, and three words: "Buenas noches, amigo!" Vance's reaction was exactly the opposite.

She and her second husband were dining out when they heard Frawley had died. Upon receiving the news, Vance reportedly shouted, "Champagne for everybody!"

Frawley is buried in the San Fernando Mission Cemetery in Mission Hills, Los Angeles, California.