The Broncos also got help from special teams, which blocked two field goals and forced a fumble on a punt return, and a defense that rebounded after getting torched a week ago in a 41-40 loss against longtime rival Fresno State.
The offense for Boise State (3-2, 1-1 Mountain West Conference) started slowly, going three-and-out on its first two possessions. But Southwick, with the help of some big runs by Aaron Baltazar and Jay Ajayi, got things rolling, putting up points on nine of their next 10 possessions en route to the most lopsided of Boise State's four straight victories over Southern Miss since 2007.
Southwick was sharp again, completing 19 of 23 passes before heading to the bench in the third quarter. He threw touchdown passes of 42, 18 and 14 yards and his 52-yarder to Geraldo Boldewijn set up Ajayi's 4-yard TD run just before the half.
Boise State rolled up 545 yards on offense and had seven different players score touchdowns. Matt Miller led Boise State with five catches for 107 yards and a touchdown and Boldewijn had 104 yards and a TD on three catches.
The defense picked off two Southern Miss passes, had four sacks and rebounded impressively after Fresno State quarterback Derek Carr passed for 460 yards and four touchdowns in leading the Bulldogs to a fourth-quarter comeback victory last week.
It was another night of futility for the Golden Eagles (0-4), losers of their last 16 games dating back to last season's opener and currently the nation's longest FBC losing streak.
Southern Miss put up 266 yards of total offense and quarterback Allan Bridgford completed 18 of 30 passes for 143 yards and two interceptions. But when the Golden Eagles defense failed to find a way to stop Boise State's offense, the game got out of control early.
The Golden Eagles pulled within 10-7 early in the second quarter when Bridgford fired a 5-yard TD pass to Marquise Ricard all alone in the back of the end zone. The short scoring drive was set up when backup quarterback Grant Hedrick fumbled a snap and Octavius Thomas pounced on a loose ball at the Boise State 8-yard line.
But Southwick and the rest of the offense didn't waste much time getting those points right back.
With the help of two Southern Miss penalties, Boise State took the ball right back down the field, setting up Southwick's 42-yard TD strike to Boldewijn, putting the Broncos up 17-7.
Bridgford led the Golden Eagles back into Bronco territory on the ensuing possession, but the drive stalled just outside the red zone, forcing a field goal attempt. But Corey Acosta's 38-yard field goal attempt was blocked by Demarcus Lawrence, his second of the game. Cornerback Donte Deayon scooped up the bouncing ball and raced to the Southern Miss 27-yard line.
Four plays later, Southwick rolled out and fired a 14-yard touchdown pass to Shane Williams-Rhodes to put the Broncos up 24-7 with 3:52 left in the half and the rout was on.