Jane Nebel and Jim Henson worked together on the live 1950s television show Sam and Friends, where Jane collaborated with Jim in performing Muppets and devising several of the show's technical innovations, including the use of television monitors to watch their performances in real time. When, in the late 1950s, Jim took a year off from Sam and Friends to travel in Europe, Jane ran the show, with the help of a UMD classmate.
"Among the first of his assignments at WRC was Afternoon, a magazine show aimed at housewives. This marked his first collaboration with Jane Nebel – the woman who later became his wife" They did not begin dating until Jim returned from Europe where he traveled for several months, to be inspired by European puppeteers who look on their work as an art form. They were married in 1959.
Their first child, Lisa, was born the next year, followed by four others: Cheryl (born 1961), Brian (born 1963), John (1965–2014) and Heather (born 1970). When she quit full-time puppeteering in the early 1960s to raise their children, Jim hired Jerry Juhl and Frank Oz to replace her. She helped the newly hired Frank Oz learn how to lip sync, and continued to perform non-speaking muppets on Sesame Street from time to time through at least the eighties. She was also responsible for the hiring of puppeteer Steve Whitmire (who would later take over performing Kermit the Frog and Ernie of "Sesame Street" after the death of Jim Henson in 1990) in 1978 after he gave her an impromptu audition in an Atlanta, Georgia airport restaurant.
In 1990 the Henson Company went into an agreement with Disney to present a live stage show: Here Come The Muppets, at Disney/MGM Studio. Jane was the key player in the development of training and profile development for the walk-around versions of the Muppets. She was able to share the Henson spirit of the ten characters that joined Disney at the time: Kermit, Miss Piggy, Fozzie Bear, Gonzo the Great, Bean Bunny, as well as five members of the Electric Mayhem Band.