Summitt is just the fourth men's or women's coach in Division I with 800 victories behind North Carolina's Dean Smith, Kentucky's Adolph Rupp and Jim Phelan at Mount Saint Mary's.
Summitt's record stands at 800-161 in 29 seasons with six national championships, second only to John Wooden's 10 titles at UCLA.
Tennessee (12-3) didn't allow for much suspense in whether Summitt would have to wait for the next game to reach the milestone.
After the Blue Demons (12-4) tied it at 2 in the opening minute, it was all Tennessee. The Lady Vols slowly built a lead and then went on an 18-0 run in the first half.
Reserve Brittany Jackson started it with two consecutive 3-pointers. Loree Moore caught a pass behind her, dribbled it around her back and drove to the basket and then Tye'sha Fluker capped the run on a putback that gave Tennessee a 36-10 lead with 5:19 remaining before halftime.
The Lady Vols' lead didn't drop below 19 points the rest of the way.
As the last seconds ticked away, the fans rose to their feet and chanted, "800, 800, 800!"
When the game ended, Summitt walked over and hugged DePaul coach Doug Bruno then hugged each player as orange and white confetti rained on the court.
Ashley Robinson led Tennessee in scoring with 12 points while Shyra Ely had 11 and Gwen Jackson added 10.
The Blue Demons were led by Khara Smith's 18 points and Charlene Smith's 14.
Despite the lopsided score, the Lady Vols didn't hold back. Summitt continued to substitute players and yell out directions and encouragement from the bench.
Summitt was hired as a graduate teaching assistant and women's coach at Tennessee in 1974 at age 22. She earned her first career victory in the team's second game in January 1975.
It took Summitt nearly four years to reach her 100th win on Jan. 13, 1979, at North Carolina State.
Summitt picked up No. 500 against Ohio State at the inaugural State Farm Tip-Off Classic in Jackson, Tenn., in 1996.
The Lady Vols won 85-62 at Wisconsin on Dec. 5, 1999, as Summitt joined Texas coach Jody Conradt as the only two women's college basketball coaches to reach 700 wins. Conradt now trails Summitt with 797 wins.