The Africans led 15-12 with less than three minutes to go in the first quarter when American coach Mike Krzyzewski sent a fresh crew of Russell Westbrook, Kevin Love, Carmelo Anthony, Deron Williams and Andre Iguodala on to the court.
The new line-up then reeled off the last nine points of the quarter to turn the deficit into a 21-15 advantage.
"A lot of times when you're watching games you pick up on things," Williams said. "Our game plan was to switch and deny but we weren't really denying them the ball.
"Then we wanted to get out in transition and run. We just tried to pick up the tempo and momentum of the game."
Tunisia, led by power forward Makram Ben Romdhane, stubbornly kept close, pulling within 35-30 in the second quarter before the Americans put on another burst to lead 46-33 at the intermission.
Ten points in a row to start the second half put the game out of reach and the US team proceeded to put on a thunderous display of dunking, with LeBron James, Westbrook, Iguodala and most notably Anthony Davis putting on a show.
The 19-year-old Davis, the only US player without NBA experience, rattled the rim with three slam dunks and scored 12 points in just under 12 minutes.
"It was real fun just playing with these guys," said Davis, the first pick of the NBA draft by the New Orleans Hornets.
"I came out of the game after a minute and a half and Melo (Carmelo Anthony) said, 'Leave him in coach. What are you taking him out for'?".
Tunisia coach Adel Tlatli said he was proud of the way his team played in the first half and saluted the US for not trying to embarrass his players.
"They could have absolutely taken us to the cleaners," he said through an interpreter. "But coach K's discipline made sure that didn't happen and they played with dignity and for that we're very grateful."
Ben Romdhane led Tunisia (0-2) with 22 points and 11 rebounds.
"Ben Romdhane played a magnificent game," Krzyzewski said. "He played with great heart. In the second half our defence picked up."
The US improved to 2-0 in the preliminary round, joining 2008 silver medallists Spain, Russia and Brazil on that mark.
In Group B, Spain beat Australia 82-70, Russia defeated China 73-54 and Brazil overcame Britain 67-62.
Australia, China and Britain all have 0-2 records.
France have a 1-1 record in Group A after defeating Argentina, who are also 1-1, by a 71-64 scoreline in a game featuring the first duel between long-time San Antonio Spurs team mates Tony Parker and Manu Ginobili.
Parker led France with 17 points while Ginobili had 26 points for Argentina.