Breida added a 61-yard score in the fourth quarter. Georgia Southern (6-2, 5-0 Sun Belt Conference) set a season high with 613 yards rushing in the first meeting of the new conference rivals.
Quarterback Kevin Ellison ran for 115 yards with a touchdown. L.A. Ramsby added 92 yards rushing with two touchdowns.
The Eagles led only 27-17 at halftime. The Panthers couldn't stay close as Georgia Southern used the nation's top-ranked running attack to put the game away with three third-quarter touchdowns.
The 69 points topped a 63-7 loss to Alabama in 2010 as the most allowed in Georgia State history.
Georgia Southern was the visiting team but asked its Atlanta-area alumni and south Georgia fans to take over the facility with a ''whiteout.'' White shirts filled about one half of the lower section of seats.
Georgia Southern fans chanted ''GSU! GSU!'' as the Eagles added to an already big lead in the fourth quarter.
Harden tied a school record with 11 catches and set Georgia State marks with 186 yards receiving and four touchdowns. Arbuckle completed 24 of 38 passes for 408 yards with four touchdowns and one interception.
Each team had only one punt in the first half.
As expected, Georgia Southern kept the ball on the ground. The Eagles lead the nation with their average of 372 yards rushing per game and used a combination of triple-option trickery and simple straight-ahead power runs to hold the ball.
Breida, Ellison, Ramsby and Zach Walker ran for touchdowns as Georgia Southern led by 10 points at halftime. Walker's 19-yard run was the only scoring play longer than 9 yards for the Eagles.
Breida then broke free for the 75-yard touchdown run on the Eagles' first snap of the second half. Breida took the option pitch from Ellison, ran right and found open field after turning the corner.
Georgia State, which has the nation's 21st-ranked passing attack, also relied on its strength as Arbuckle threw scoring passes of 3 and 59 yards to Harden in the first half.