Scott has worked on the Tigers' staff since 2008 and was a finalist for the Broyles Award (top assistant coach) in 2018.
"I have great respect for the USF football program and what has been accomplished in a very short time and can't wait to get to work building on that foundation to produce a championship program," Scott said in a statement announcing his hiring. "... It is difficult to leave my alma mater and the great program we have built at Clemson, but I believe we can do great things at USF. I am thankful to Coach (Dabo) Swinney and all the Clemson players and staff for the great experiences and lessons that have prepared me to lead USF football."
Swinney released a statement in which he confirmed Scott will rejoin Clemson for the duration of its College Football Playoff run and said he would like to "thank Jeff Scott for a wonderful 12 years."
"Our team is excited that he'll have the opportunity to finish our 2019 season with us," Swinney said in the statement. "Jeff has been with me since day one when I became interim. He's somebody I trust immensely and he's extremely loyal. He's been patient for the right opportunity, and I think this is that right opportunity."
Scott is the first Clemson coordinator to leave during the team's historic five-year run that includes five straight CFP appearances and two national titles.
"Jeff is a very bright, enthusiastic and driven leader for our program and we are thrilled to welcome him to USF and back to Florida, where he was born and where he has recruited so well for Clemson for many years," South Florida athletic director Michael Kelly said in the statement. "He is a young and extremely gifted offensive mind, a developer of high-level talent and an elite national recruiter who brings the experience of having played an integral role from the beginning in helping to build one of the most successful programs in college football.
South Florida is replacing Charlie Strong, who was fired earlier this month after he went 21-16 in three seasons but had a 4-14 record over the Bulls' past 18 games.
South Florida athletic director Michael Kelly had set a Dec. 18 deadline -- the national early signing date -- to hire a new coach.
Florida tight ends coach Larry Scott also was considered for the job.