Cole Fisher booted three field goals, including a 33-yarder to end the first half, to provide the needed cushion for the victory. He hit from the 39-yards out and added a 41-yarder with 4:37 left in the game for a 30-21 lead.
Riddle found Stephen Houzah in stride for a 73-yard scoring strike to take a 27-14 lead in the fourth.
Mercer (2-1, 1-0) was thrashed by Memphis 66-14 in the season opener, then beat Jacksonville 45-3 before snapping an eight-game losing streak to the Bulldogs. Mercer last beat Samford in 1932.
Tee Mitchell rushed for 103 yards and Marquise Irvin grabbed six tosses for 71 yards.
Devlin Hodges threw for 291 yards with three touchdowns as the Bulldogs (1-2, 0-1) closed to 27-21 midway in the final quarter.