Wilson began his radio career as a singer over Denver radio station KFEL in 1923. By 1929, he was working at KFI in Los Angeles. Though best known for his comedy work with Benny, Wilson had a background as a sportscaster, covering the opening of the 1932 Summer Olympics. Wilson first worked with Benny on the broadcast of April 6, 1934, concurrent with a short stint as announcer onGeorge Gershwin's series, Music by Gershwin. At 6 feet (1.83 m) and over 200 pounds (91 kg), Wilson possessed a resonant voice, a deep belly laugh, and a plump figure, all of which would become important parts of his character with Benny. Though Wilson's primary function as announcer was to read the opening and the commercial pitches — notably for Jell-O, Grape-Nuts, and Lucky Strikes — his importance to the program was as both feed and foil to Jack and other cast members. A recurring goal was his effort to get the Sportsmen Quartet singing commercials approved by Benny.
On radio in particular, Wilson's girth could be exploited, both in jokes by Benny and in audio gags, such as the amount of time it took a railroad porter to brush the soot off of Don following a train trip, or to measure charging him by the pound.
Wilson rarely flubbed his lines. His most famous incident occurred on the January 8, 1950 broadcast. The script called for him to refer to columnist Drew Pearson, but Wilson read the name as "Dreer Pooson." Later on in the broadcast, during a murder-mystery skit, Frank Nelson took advantage of the situation. Benny asked Nelson, "Pardon me, are you the doorman?" and Nelson, in his customary sarcastic manner, came back with: "Well who do you think I am, Dreer Pooson?," to sustained laughter and applause.
Wilson also served stints as announcer for radio comedy or variety shows starring Alan Young, Bing Crosby, Ginny Simms, and Fanny Brice's comedy hit Baby Snooks. In 1946, Don Wilson was a regular on the daytime comedy Glamour Manor, opposite former Jack Benny Program regular Kenny Baker.
Wilson accompanied Benny into television in 1950, remaining with him through the series' end in 1965. On television, the fat jokes were toned down only slightly, mostly because the real Wilson was not as impossibly large as the radio Wilson was described. These appearances also often involved the fictional character of Don's equally hefty, aspiring announcer son, Harlow (played by Dale White). Wilson also co-starred with Benny in Buck Benny Rides Again (1940) and voicing a caricature of himself in The Mouse that Jack Built, a 1959 Warner Brothers spoof of The Jack Benny Program directed by Robert McKimson.
Other film roles included small appearances as announcers or commentators in several films, providing narration for Walt Disney's Academy Award nominated short Ferdinand the Bull, and a credited appearance as Mr. Kettering opposite Marilyn Monroe in Niagara. Wilson did frequent commercials and appeared in the Western Union Candygram commercials as their spokesman from 1969 through 1971. Those who recall the commercial remember him blaring out "Just tell them I want to send a Candygram."
His final on-camera appearance in a series was in two episodes of the 1960s Batman as newscaster Walter Klondike (spoofing Walter Cronkite). Wilson would continue to appear on talk-shows throughout his life whenever a program would salute Jack Benny or talk about old-time radio.
Wilson played football for the University of Colorado in the 20's. For his size he was an excellent sportsman, and was an excellent amateur golfer teaming up with fellow NBC announcer Bud Stevens to win many matches in Southern California. Wilson was married four times. His second wife was Peggy Ann Kent, daughter of 20th Century Fox President Sidney R. Kent. They were married November 19, 1940 and divorced in December, 1942. The same month the divorce was final, Wilson married Polish countess Marusia Radunska. This marriage ended in divorce in 1949. Wilson finally found a lasting partnership with fourth wife, radio actress Lois Corbet (who occasionally appeared as "Mrs. Wilson" on Benny's later radio and TV shows). Together they hosted a local Palm Springs, California television show Town Talk from 1968 until the mid-1970s.
Wilson and his wife lived in Palm Springs after his retirement.