Watford was 22 of 37 for 345 yards and Mixson had 135 receiving on seven catches.
The Pirates raced to a 21-3 halftime lead behind three scoring passes from Watford, two to Mixson and an 18-yarder to Dewayne Garrett.
The Thorobreds scored touchdowns on consecutive drives early in the third. Ora Johnson found Reginal Harris from 19 yards and ran seven for another score to cut the lead to 21-17 with 7:14 left in the quarter.
Hampton responded with a nine-play, 68-yard drive capped by a 25-yard touchdown pass from Watford to Mixson to make the score 28-17. Watford's 55-yard touchdown to Mixson in the fourth quarter iced it.
Kentucky State's Kyle Jackson had 93 yards rushing and Jermaine Graham had two of Watford's three interceptions.