The defending champions rolled to a 156-73 victory, scoring the most points ever in an Olympic game on a mind-boggling shooting night spearheaded by Carmelo Anthony.
Anthony made 13 of his 16 shots, including an incredible 10-of-12 from beyond the three-point line for a 37-point haul.
The points total easily eclipsed the previous record of 138 set by Brazil in 1988. The US half-time total of 78 points was also an Olympic record, officials said.
"Every time that I touched it, the ball was going in as far as the zone that I was in," Anthony said.
The entire US team, given a wide berth by Nigerian defenders, enjoyed an extraordinarily accurate night of target practice as they made 71 per cent of their shots, including 29-of-46 from long range, and 30-of-37 from inside the arc.
"We shot better than any team in a game I ever coached. Our guys just couldn't miss tonight," US coach Mike Krzyzewski said.
His Nigerian counterpart Ayodele Bakare could only shake his head in disbelief at the US performance. "They shot an unbelievable percentage. I felt we could have played better defensively," he lamented.
The victory improved the US to 3-0 in the preliminary round while Nigeria slipped to 1-2.
Kzyzewski bristled, however, when he was asked at the post-game news conference whether he felt his team had been cruel to humiliate an overmatched opponent.
"We didn't play LeBron (James) and Kobe (Bryant) in the second half. We benched Melo (Anthony) despite how he was playing. We didn't play (Kevin) Durant. We didn't take any fast breaks. There is a 24-second clock. The shots we took, we happened to hit," he said.
"A coach would think it humiliating if we didn't play hard. We just want to play hard and win."
Ike Diogu, who played six seasons with various NBA clubs, led Nigeria with 27 points.
"When they shoot like this, I don't think there is any team that could beat them," Diogu said.
Nigerian forward Koko Archibong said it was quite an experience being part of the game.
"On the one side, it's terrible to get whupped like that," he said. "But on the other side it was something impressive to see, to be a part of, to witness in person."
Vitaliy Fridzon's fadeaway three-pointer from the corner while falling down with four seconds left lifted Russia to a thrilling 75-74 win over Brazil.
The scintillating preliminary round duel between unbeaten teams came down to a seesaw battle over the final seconds that lifted Russia to 3-0 and dropped Brazil to 2-1 in the chase for quarter-finals seedings in Group B.
"They hit a very tough shot. Maybe if they shoot it 10 times he wouldn't make it again," said Brazilian captain Marcelinho Huertas. "He was falling and a guy was under his foot. We have to forget this right away."
The stage was set when Russia overcame a 70-65 lead taken by Brazil after the South Americans had trailed 59-53 going into the fourth quarter of the taut contest.
A three-pointer by Russia's Alexey Shved with 40 seconds left tied the game at 72-72.
Huertas knifed through the lane and spun in a left-handed layup with 6.1 seconds left for a 74-72 lead on a drive that appeared to put Brazil in control.
Russia called timeout, and their American coach David Blatt drew up a play they had not practiced.
The ball swung over to Fridzon, who had scored only three points in the game at that point. He took the pass and instantly launched his jump shot as defender Leandro Barbosa undercut him and sent him sprawling to the floor.
The ball swished through the net with four seconds left and Russia were winners in the most exciting men's game so far.
"Good for him, really good for him," Blatt said about Fridzon, whose basket made the Olympic Basketball Arena crowd gasp before erupting in cheers. "He made the coach look good.
"He had to catch and release the ball quickly. More important than the play was the execution. They executed it to perfection."
Andrei Kirilenko led Russia with 19 points, Timofey Mozgov had 18 and Shved scored 17. Barbosa led the way for Brazil with 16 points.
The hard-fought contest saw several swings of momentum, but the game always seemed headed for a dramatic climax.
"Certainly, we were no more deserving of that game than Brazil was. It was a joy to be a part of that. It was wonderful," said Blatt, before conceding, "It's a heck of a lot easier to talk like this when you win."
In other preliminary round games, France (2-1) beat Lithuania (1-2) 82-74, Argentina (2-1) beat Tunisia (0-3) 92-69 and Australia (1-2) defeated China (0-3) 81-61.