Wexner was born to a Jewish family[2] in Dayton, Ohio,[3] the son of Bella (née Cabakoff) and Harry Wexner.[4] He has one sister, Susan.[4] He attended Ohio State University, majoring in business administration.[3] He became a member of Sigma Alpha Mu fraternity. He briefly attended the Moritz College of Law.

Wexner started working in his parents' clothing store. While they were away on vacation he analyzed the profit and loss margins on the Women's clothing that they sold. He found that although higher priced clothing (e.g. jackets) cost more money, they sold less often than blouses which sold at a faster rate. When he told his father this, his father was not interested in changing his inventory.[5] In 1963, Wexner was loaned $5,000 from his aunt to start The Limited (so named because the store focused on a limited amount of merchandise that turned over quickly and had a higher profit margin, unlike his parent's store).[5] The Limited opened its first store in the Kingsdale Shopping Center in Upper Arlington. Wexner's parents closed their store one year later and joined their son at The Limited. Wexner took Limited Brands public in 1969, listed as LTD on the NYSE. Wexner is the longest serving CEO of a Fortune 500 company.[6] Wexner was ranked #11 on Harvard Business Review’s Top 100 Best Performing CEOs of 2015, and #34 in 2016.