Helfrich, the team’s former offensive coordinator, was promoted when Chip Kelly left the Ducks in January for the NFL’s Philadelphia Eagles.
Nicholls’ score came on Andrew Dolan’s 35-yard field goal in the second quarter.
Quarterback Beaux Hebert made his first start for the Colonels, but was hit hard by Oregon cornerback Terrance Mitchell late in the first quarter and left the game. Mitchell was flagged for targeting and ejected.
Oregon finished 12-1 last season and defeated Kansas State 35-17 in the Fiesta Bowl. The Ducks’ offense averaged 49.5 points per game, second in the nation, and was among the top five in rushing (315.2 yards per game) and in total yards (537.4 yards per game).
The Ducks were only barely challenged by Nicholls, a Southland Conference program from Louisiana which has won just one game in each of the past two seasons. The Colonels had never played a team ranked in the top five.
On its first drive Oregon scored on a 4-yard run by Thomas. On its next, Mariota found Bralon Addison with a 27-yard scoring pass to make it 14-0.
Thomas added a 22-yard scoring run with 6:28 left in the first quarter and Alejandro Maldonado kicked a 29-yard field goal to make it 24-0.
Mitchell was ejected when he hit Hebert, who was sliding on the turf, and the replay showed helmet-to-helmet contact.
Under a new NCAA rule this season, players who “target” and contact defenseless players will receive a 15-yard penalty and be ejected.
Hebert, the son of former New Orleans Saints quarterback Bobby Hebert, did not return after the hit and was replaced by junior Kalen Henderson, a transfer from Tulsa.
Hebert and Henderson battled for the starting job during fall camp after projected Nicholls starter Landry Klann required offseason shoulder surgery.
Hebert, making his first career start, completed four of 10 passes for 42 yards before he left the game.
Shortly after the ejection, Nicholls avoided the shutout with Dolan’s 35-yarder to make it 24-3.
Mariota ran for a pair of touchdowns, the first from 12 yards and the second from 46, to put the Ducks up 38-3 at the half.
The sophomore quarterback, who was on several Heisman watch lists going into the season, was selected to the Pac-12 first team last season and earned conference Freshman of the Year honors.
Byron Marshall ran for a 49-yard touchdown for the only third-quarter score, and Oregon blocked Dolan’s 42-yard field-goal attempt early in the fourth.
Colt Lyerla scored on a 3-yard run and quarterback Jeff Lockie — who took over for Mariota in the fourth quarter — added an 8-yard TD run before he was subbed out for quarterback Jake Rodrigues, who found Chance Allen in the end zone with a 23-yard pass for the final margin.
Thomas also sat out the final quarter. Last season, he ran for 701 yards and 11 touchdowns and caught 45 passes for 445 yards and five more scores. He also scored on a kickoff return and a punt return, becoming the first Oregon player in 47 years with a touchdown four different ways.
Marshall finished with 124 yards rushing, giving Oregon its first game to feature three players with more than 100 yards rushing.
The Colonels’ last game was also in the state of Oregon. Nicholls State lost 77-3 to Oregon State in Corvallis on Dec. 1. The game, Nicholls State’s first against a Pac-12 foe, was originally scheduled as the season opener, but it was delayed when Hurricane Isaac approached Louisiana.