Leitao's deal with DePaul is for five years, sources told ESPN. An introductory news conference has been scheduled for Monday afternoon.
"This is a special day for my family and me," Leitao said in a statement released by the school. "I underestimated what a special place DePaul University and the city of Chicago are when I left here in 2005. The dedication and support here to the growth of student success is second to none, not only for a basketball program but also for the entire student body.
"I'm proud and our team will be proud to represent this great institution in one of the world's great cities. We will exude the work ethic that drives Chicago and the region every day and look forward to everyone joining us next season."
In each of Leitao's three seasons coaching DePaul from 2002 to 2005, the Blue Demons reached the postseason, making the NCAA tournament in 2004 and the NIT in 2003 and 2005. The Blue Demons haven't been back to the NCAA tournament since Leitao's tenure.
"His success here speaks for itself with three postseason appearances in three years with teams that energized our alumni and fans with their competitiveness and work ethic," athletic director Jean Lenti Ponsetto said in the statement.
"When he left in 2005, we recognized that it is the nature of our business that dynamic coaches get recruited away. Now we are pleased to welcome Dave, his wife Joyce and their family back to Lincoln Park with great enthusiasm for his leadership and the future development of our men's basketball program."
Leitao left DePaul to coach Virginia for four seasons before coaching in the D-League and then becoming an assistant to Frank Haith at both Missouri and most recently Tulsa.
Leitao also was a head coach at Northeastern for two seasons in the 1990s, going 22-35 overall, between stints as an assistant under Jim Calhoun at UConn.
DePaul finished 12-20 (6-12 Big East) this season, leading to coach Oliver Purnell's resignation earlier this month.