Chattanooga (2-2, 1-0) ran up a 24-3 halftime lead. After Warren Handrahan's 19-yard field goal for Samford, Williams broke off a 34-yard touchdown run on the Mocs' first possession, Henrique Ribeiro made a 31-yard field goal and Tommy Hudson returned a punt 66 yards for another TD - all before the end of the first quarter.
Jacob Huesman's 1-yard touchdown plunge provided the 17-point margin at intermission.
Samford pulled within a touchdown in the third. A 39-yard pass completion from Michael Eubank to Karel Hamilton set up Denzel Williams' 9-yard touchdown scamper and on the next possession, Eubank found Hamilton for a 24-yard scoring pass.
But Williams and Huesman added fourth quarter touchdowns runs to seal the win, though Eubank found Hamilton for a 23-yard score late. Hamilton had 129 yards on six catches.