He started in aviation by buying a Jenny and then an Alexander Eaglerock, and joined Tex Rankin's Flying Circus in Portland, Oregon. He went to Dallas and worked for Fairchild Aerial Surveys, photographing the Mississippi Delta surrounding New Orleans.
In 1930, he went to work for Varney in Portland, Oregon and then joined Boeing Air Transport as a co-pilot, he didn't get much flying time and he returned to Fairchild. When the Great Depression lifted, Jeppesen delivered mail in a Boeing 40B. Jeppesen realized that someone would have to develop flying charts to replace the road maps used by pilots. He compiled information on objects visible from the air. He designated landmarks, elevations of obstructions and airport runway information to help him on his mail runs. After several pilots borrowed his information, he decided to print copies of the charts and allow pilots to buy the manual for $10 each. In 1936, he married Nadine and together they worked on the charts at their home in Salt Lake City. He moved to Denver in 1941, and rented office space to hold the expanding business. Jeppesen continued to fly for United Airlines while the manual business was growing.