[2][7][8][9] Johnson's fashion career started after she entered and won the Mademoiselle Guest Editor Contest.

In 1969, she opened a boutique called Betsey Bunky Nini on New York City's Upper East Side.

[citation needed] In the 1970s, Johnson took control of the fashion label "Alley Cat" which was popular with the rock 'n roll musicians of the day.

[5] She designed the dress that Lisa Loeb wore in the music video for her 1994 hit "Stay (I Missed You)".

[citation needed] In September 2010, her Spring/Summer 2011 Ready-to-Wear fashion show generated a lot of buzz before it started because models were rumored to come down the runway riding bicycles.

[15] However, the original concept proved too dangerous during the rehearsals,[16] so Betsey asked model Kim Matulova to ride a skateboard while wearing open-toed platform heels instead.

[18] On September 12, 2012, she celebrated 40 years of her brand with a retrospective fashion show with Cyndi Lauper performing.

[23] In 2022, Johnson appeared on RuPaul's Drag Race All Stars as a guest judge (Episode: "Legendary Legend Looks").