The breakout came after two games that fell below his rushing average last season.
''I haven't been frustrated,'' he said. ''It's going to happen, you know? Eventually it's going to happen.''
James' 90-yard dash was Oregon's longest run since 1938. He added a 1-yard TD run in the first quarter and a 50-yarder in the third.
The long one was really the result of the Ducks' offensive line, James insisted, and the path that was cleared by wide receiver Justin Hoffman - who dramatically pushed aside two defenders.
When asked when he knew he was going to score, the speedy running back responded: ''When I got into the end zone. Seriously.''
James has 42 career touchdowns, matching the school record set by Derek Loville (1986-89).
Missouri State (0-3) scored on its first possession. The Bears were efficient in a nine-play, 84-yard drive that was capped by Chris Douglas' 3-yard touchdown run to make it 7-0. By halftime, though, the Ducks were ahead 35-7.
Trevor Wooden completed six of 13 passes for 91 yards, and ran for 67 yards. He said the issue was keeping up with the bigger, stronger and faster Ducks.
''We showed what we could do at the beginning,'' he said.
It was the Ducks' 18th straight victory at Autzen Stadium.
Before the game, Oregon announced it had received a formal notice of inquiry from the NCAA regarding its use of recruiting services. The investigation was prompted by questions raised over a $25,000 payment Oregon made to Willie Lyles and Houston-based Complete Scouting Services.
''We didn't address it at all with our football team. We've been aware the NCAA's been examining and reviewing us for a while now,'' coach Chip Kelly said afterward.
Saturday's opponent was supposed to be Utah, but that game was changed because of the Pac-12 realignment. Oregon was left scrambling for an opponent, and the Bears stepped in.
Missouri State will be paid $440,000 for visiting Autzen Stadium. The Bears also visited Arkansas in their opener and made $395,000 in a 51-7 loss.
Coach Terry Allen said it's his job to make sure the Bears' morale hasn't suffered because of the tough schedule. Missouri State opens Missouri Valley Conference play at Southern Illinois next Saturday.
The Ducks will visit Arizona in their Pac-12 opener next week.
Oregon scored twice in the first quarter on James' 1-yard run and Thomas' 8-yard scoring pass to Tuinei.
Oregon freshman De'Anthony Thomas topped 100 all-purpose yards in the first quarter on one punt return, one kickoff return, one run and a reception.
Oregon made it 21-7 on Thomas's 7-yard touchdown pass to freshman Colt Lyerla, on a drive that spanned 93 yards on three plays in 37 seconds.
While that was fast, it couldn't compare to James' 90-yard scoring run a short time later. That drive took all of 13 seconds. The longest run in school history was Bob Smith's 92-yarder against Idaho in 1938.
Thomas' second scoring pass to Tuinei came with 5:33 to go before the half. Thomas matched a school record with six touchdown passes the week before in a 69-20 victory over Nevada.
James opened the second half with a 50-yard scoring run.
The running back had been held to 54 yards in Oregon's season-opening 40-27 loss to then-No. 4 LSU. Then last week against the Wolf Pack he ran for 67 yards, but scored on a run, a reception and a punt return.
James averaged more than 144 yards rushing a game last season. After Saturday's performance, he upped his average this season to 108.3 yards.
Oregon backup Bryan Bennett hit Lyerla with a 26-yard TD pass, and Eric Dungy with a 22-yard scoring strike to make it 56-7 in the third quarter after the starters left. Dungy, a redshirt freshman, is the son of former NFL coach Tony Dungy.
Kiko Alonso got the start at linebacker for the Ducks, a week after coming off suspension for offseason legal trouble. Alonso started in place of Michael Clay, who injured his ankle last week.
Cornerback and kick returner Cliff Harris, also reinstated last week from an indefinite suspension, came into the game in the second quarter.
Missouri State, which hadn't been 0-3 since 1994, had never played the Ducks.