Garrison Keillor started his professional radio career in November 1969 with Minnesota Educational Radio (MER), now Minnesota Public Radio (MPR) and distributing programs under the American Public Media (APM) brand. He hosted The Morning Program in the weekday drive time slot of 6 to 9 a.m. on KSJR 90.1 FM at St. John's University in Collegeville, which the station called "A Prairie Home Entertainment." The show's eclectic music was a major divergence from the station's usual classical fare. During this time he also began submitting fiction to The New Yorker, where his first story, "Local Family Keeps Son Happy," appeared on September 19, 1970.
Keillor resigned from The Morning Program in February 1971 to protest what he considered an attempt to interfere with his musical programming. The show became A Prairie Home Companion when he returned in October.
Keillor has attributed the idea for the live Saturday night radio program to his 1973 assignment to write about the Grand Ole Opry for The New Yorker, but he had already begun showcasing local musicians on the morning show, despite limited studio space for them, and in August 1973 The Minneapolis Tribune reported MER's plans for a Saturday night version of A Prairie Home Companion with live musicians.
A Prairie Home Companion debuted as an old-style variety show before a live audience on July 6, 1974, featuring guest musicians and a cadre cast doing musical numbers and comic skits replete with elaborate live sound effects. The show was punctuated by spoof commercial spots from such fictitious sponsors as Jack's Auto Repair ("All tracks lead to Jack's where the bright shining lights show you the way to complete satisfaction") and Powdermilk Biscuits, which "give shy persons the strength to get up and do what needs to be done." Later imaginary sponsors have included Ralph's Pretty Good Grocery ("If you can't find it at Ralph's, you can probably get along without it"), Bertha's Kitty Boutique, the Ketchup Advisory Board (which touted "the natural mellowing agents of ketchup"), the American Duct Tape Council, and Bebop-A-Reebop Rhubarb Pie ("sweetening the sour taste of failure through the generations"). The show also contains parodic serial melodramas, such as The Adventures of Guy Noir, Private Eye and The Lives of the Cowboys. After the show's intermission, Keillor reads clever and often humorous greetings to friends and family at home submitted by members of the theater audience in exchange for an honorarium.
Also in the second half of the show, the broadcasts showcase a weekly monologue by Keillor entitled The News from Lake Wobegon. The town is based in part on Keillor's own hometown of Anoka, Minnesota, and in part on Freeport and other towns in Stearns County, where he lived in the early 1970s. Lake Wobegon is a quintessential but fictional Minnesotan small town "where all the women are strong, all the men are good-looking, and all the children are above average." A Prairie Home Companion ran until 1987, when Keillor decided to end it; he worked on other projects, including another live radio program, "The American Radio Company of the Air"—which had almost the same format as A Prairie Home Companion's—for several years. In 1993 he began producing A Prairie Home Companion again, in a format nearly identical to the original's, and has done so since. On A Prairie Home Companion, Keillor receives no billing or credit (except "written by Sarah Bellum," a joking reference to his own brain); his name is not mentioned unless a guest addresses him by his first name or the initials "G. K.," though some sketches feature Keillor as his alter ego, Carson Wyler.
A Prairie Home Companion regularly goes on the road and is broadcast live from popular venues around the United States, often featuring local celebrities and skits incorporating local color. Keillor also sometimes gives broadcast performances of a similar nature that do not carry the "Prairie Home Companion" brand, as in his 2008 appearance at the Oregon Bach Festival. In March 2011, Keillor announced that he would be retiring from "A Prairie Home Companion" in 2013.