SMU (12-4, 2-2 American Athletic Conference) never trailed, scoring the first 13 points and owned a double-digit lead from four minutes after tipoff for the rest of the game. Their largest lead was 26 late with 4:16 remaining.
Kennedy, a 6-foot-9 sophomore transfer who played previously for Villanova, made his second consecutive start since SMU's starting center, 6-11 junior Yanick Moreira, injured his right knee in practice last Thursday.
Kennedy is SMU's second-leading scorer this season despite coming off the bench for the first 14 games. He made his first start last Saturday in a 71-63 loss at then-No. 12 Louisville. Moreira will be out for three to six weeks.
SMU went into the game ranked fourth in Division I in field-goal defense, allowing 36.5-percent shooting, and held South Florida to 32.1 percent.
SMU raced to the 13-0 lead in the first 4:39 while South Florida missed its first six field-goal attempts and committed three turnovers.
The Mustangs were so hot they missed a free-throw attempt before missing from the field -- and got the offensive rebound on the missed free throw to convert it into a basket.
When USF freshman guard Josh Heath sailed an intended alley-oop pass out of bounds, SMU came down court and responded with a successful alley-oop from Williams to Kennedy.
The SMU first-half lead reached 19 points with 7:04 left before intermission at 30-11.
USF played its seventh consecutive game without junior point guard Anthony Collins, a three-year starter sidelined with knee problems.
Zach LeDay led South Florida (10-7, 1-3), with 12 points off the bench.
Maryland point guard Melo Trimble, considered a lock to leave the program before struggling in the second half last season, has withdrawn from the NBA draft and will return for his junior season.
Louisville's Chinanu Onuaku, who recently underwent a medical procedure to correct a heart rhythm issue detected during the combine, will keep his name in the NBA draft pool.
Andrew White III will return to the Nebraska men's basketball team next season after removing his name from the NBA draft.