My World and Welcome to It was a half-hour situation comedy based on the writings of humorist and cartoonist James Thurber, and episodes of the show incorporated stories and cartoons by Thurber. (The program's title is also the title of a well-known collection of Thurber stories.) The show used a combination of live action and animation to represent the world of John Monroe (William Windom), like Thurber a writer and cartoonist, who worked for The Manhattanite, a magazine very much like The New Yorker, for which Thurber wrote and illustrated for many years. All the animation was based on Thurber's drawings, including the show's opening credits.

John Monroe had to contend with his hot-tempered, often obtuse boss, Manhattanite editor Hamilton Greeley (Harold J. Stone), who usually found John's cartoons incomprehensible. (Greeley was loosely based on New Yorker editor Harold Ross.) Fortunately for John, he could share his frustrations with his writer friend, the sardonic Phil Jensen (based on writer Robert Benchley and played by Henry Morgan).

At home in Westport, Connecticut, John had to contend with the women in his life, whom he spent much agony trying to understand. His wife Ellen (Joan Hotchkis) was practical and down-to-earth and was constantly bemused by John's inability to cope with day to day life, while his daughter, 10-year-old Lydia (Lisa Gerritsen), was precocious and intelligent in ways that constantly confounded John.

In addition to the innovative use of animation combined with live action, the show had several other unusual characteristics. Many of the episodes incorporated Thurber stories like "If Grant Had Been Drinking at Appomattox" or "The Unicorn in the Garden." There were many fantasy sequences, the products of John's fertile imagination, which allowed him to escape reality, much like Thurber's most famous character, Walter Mitty. The cartoons that John drew for The Manhattanite were Thurber's cartoons. And John would often turn from the action to talk directly to the camera, just as George Burns had done on The George Burns and Gracie Allen Show and Garry Shandling would do years later on It's Garry Shandling's Show.

In 1970 My World and Welcome to It won the Emmy Award for Best Comedy Series, and William Windom won Best Actor in a Comedy Series for his portrayal of John Monroe. Unfortunately, the show was cancelled after only one season. There was a great outcry when NBC cancelled the show, and there was talk of bringing the show back, but the cost of resuming production would have been too high, so that idea was scrapped.