Sinatra first sang the song on his weekly radio show in 1946 as the second part of a medley with "Easy to Love". He sang it with a big band in an arrangement by Nelson Riddle. Riddle was a fan of Maurice Ravel and said that this arrangement was inspired by the Boléro. Sinatra aficionados usually rank this as one of his finest collaborations with Riddle's orchestra. The slide trombone solo is by Milt Bernhart. Sinatra usually included the song in his concerts, —a tradition carried on by his son, Frank Sinatra Jr.
Sinatra re-recorded "I've Got You Under My Skin" for the album Sinatra's Sinatra (1963), an album of re-recordings of his favorites. This time the trombone solo was by Dick Nash because Bernhart was unavailable.
Neneh Cherry's hip-hop interpretation of the song in 1990 was the lead single for the Red Hot + Blue charity album, and reached number 25 in the UK Singles Chart. The music video was directed by Jean-Baptiste Mondino. Cherry replaced most of the lyrics with a rap on AIDS victims and how society reacts to them. Of the original Cole Porter lyrics, she kept only the first four lines and "Use your mentality, wake up to reality".