Wilson was born in Roseland near Amite, the seat of Tangipahoa Parish, one of the "Florida Parishes" of southeastern Louisiana. He began his career as a safety engineer while he traveled throughout Acadiana. The safety lectures that he made to refinery workers prompted him to become a Cajun storyteller. He remembered it this way on the back cover of The Justin Wilson Cook Book:

"Way back when I first started as a safety engineer, I took myself pretty seriously, and I found I was putting my audiences to sleep. So having lived all my life among the Cajuns of Louisiana, and having a good memory for the patois and the type of humor Cajuns go for, I started interspersing my talks on safety with Cajun humor."

Wilson later recorded several comedy albums, beginning with The Humorous World of Justin Wilson on Ember Records. He also recorded several albums for Jewel Records on the Paula label and a few for Capitol Records. He later appeared as a guest on the popular CBS series The Ed Sullivan Show. He was known for the catchphrase, "I gar-on-tee!".

As a comedian, Wilson was enormously popular in Louisiana, and to a lesser degree in neighboring states, but his humor may have been a little too specifically regional to enjoy the wider popularity of Southern comics such as Jerry Clower or Archie Campbell.

He composed ten songs, as well as composing the background music for his cooking show and recorded one album of Christmas songs with a jazz band. Wilson wrote seven Cajun cookbooks and two books of Cajun stories. He hosted several cooking shows on PBS that combined Cajun cooking and humor. Most were aired from the studios of WYES-TV in New Orleans.

Author Harnett T. Kane said of Wilson: "I know of no one [else] who portrays the Louisiana Cajun as well, so skillfully and entertainingly". A little-known fact about Justin was that his wife was the cook, not him