Amadi's pick came at the Oregon 44 and he returned it 21 yards with 2:06 left. The Ducks then ran out the clock.
New Oregon head coach Willie Taggart improved to 2-0, securing the program's first big non-conference win since 2014.
Led by cornerback Thomas Graham Jr. (two interceptions) and linebacker Troy Dye (team-high 11 tackles), the defense made numerous plays down the stretch to help secure the win.
Lee completed just 19 of 41 passes for 252 yards, with three touchdowns and four interceptions.
Oregon running back Royce Freeman rushed 29 times for 153 yards and two scores. Quarterback Justin Herbert was 25 of 33 for 365 yards, with three touchdowns and one interception.
After jumping out to a 42-14 halftime lead, the Ducks appeared to be on cruise control until Nebraska (1-1) responded with the first 14 points of the third quarter. After the Cornhuskers intercepted a pass from Herbert, they had the ball in Oregon territory and threatened to make it a one-score game.
The Oregon defense came up with a huge third-down stop when linebacker Jonah Moi sacked Lee, forcing a punt.
The Ducks got off to a fast start as they did against Southern Utah a week earlier, jumping out to a 14-0 lead after scoring on their first two possessions.
Nebraska battled back to make the score 21-14 early in the second quarter on a Tre Bryant rushing touchdown before Oregon responded with 21 consecutive points to end the half in taking a 42-14 lead at the break.
Bryant rushed 20 times for 107 yards, his second 100-yard effort of the season.