LeBron James added 16 points and Russell Westbrook had 15 for the Americans, who built a 40-point lead early in the fourth quarter. Every basket from there seemed to be a dunk.
Chicago Bulls All-Star Luol Deng scored 25 points for Britain against his former college coach at Duke.
"He said they just had never faced that speed and quickness, so you can't practice that," Mike Krzyzewski said. "You can't simulate that, so I thought it was a great experience for them. And us."
Krzyzewski inserted Kevin Durant for Anthony, and Williams for Chris Paul, and both Anthony and Williams flourished in their new roles.
Williams, who couldn't scrimmage with the Americans when they opened camp because he hadn't signed his $98 million extension with the Nets yet, made 7 of 8 shots, going 5 of 6 from 3-point range and adding five assists.
"I feel I adjusted pretty well," Williams said. "I was a little worried about how my conditioning was going to be, just because I hadn't played 5-on-5, but I just trained really hard coming in so I'd just be in the best shape possible, and I feel like I'm there."
Anthony came in for Durant in the first quarter apparently unnoticed to the PA announcer, who credited Durant with the Knicks forward's first basket and shook off the change well after being a starter in three previous years with the national team and both exhibitions this year. He rebounded from a poor game in Washington by shooting 8 of 10 from the field.
"It was fine with me, definitely fine with me," Anthony said of the change. "[Krzyzewski] came to us this morning, me and Chris, asked if we were OK with it. I'm like, 'Why wouldn't we be?' It is what it is. He wanted to put a different lineup out there against this team, see some different things. He's still trying to figure it out as a coach as well with this new group."
Britain's home game was similar to the Americans' opener against China in the Beijing Olympics, where plays for both teams were loudly cheered. The boos were brief, when a light "USA!" chant broke out in the fourth quarter.
Basketball has little place in British sports, but with the national team returning to the Olympics this year as the games' host, the sport got some attention with a visit from the powerful U.S. squad.
In an unusual pregame scene, the crowd didn't seem interested in the home team's strange set of pregame warm-up exercises, choosing instead to watch the Americans' practice dunks, oohing and aahing along the way.
The rules of the game were then shown on the overhead video scoreboard and explained by the public address announcer before play began.
The British, also including the Portland Trail Blazers' Joel Freeland and coached by Houston Rockets assistant Chris Finch, hung with the Americans for 10-plus minutes before the visitors' athleticism ran them off the floor.
"We knew what kind of level we had to get to to compete in the Olympics," British forward Kieron Achara said. "This was a level higher than we were used to."
Coming off a tough test against Brazil in an 80-69 victory Monday in Washington in which they trailed by 10 after one quarter, the Americans led by only three inside with 1 1/2 minutes left in the opening period. They closed with 10 straight points, with Anthony nailing consecutive 3-pointers that made it 33-20.
Krzyzewski went with an explosive lineup of Durant, Kobe Bryant, James and Anthony four of the NBA's top six scorers and Paul late in the second quarter, and James scored twice on feeds from Anthony and set up Durant for another basket in an 8-0 spurt that extended a 10-point lead to 18, and the game was never close again.
"It doesn't get more explosive than that, and that's the dynamic of our team," James said. "We have an opportunity to do multiple things with our lineups, and it's a luxury we have."
Durant scored 13 points and No. 1 pick Anthony Davis had 11 for the Americans, who shot 60 percent from the field and led by as much as 47.
This was possibly the Americans' last easy game before London, with exhibitions remaining in Barcelona against 2008 bronze medalist Argentina and Spain, the team they beat in the gold-medal game four years ago.
Former NBA player Pops Mensah-Bonsu scored 12 points, and Andrew Sullivan had 11 for Britain.
USA 118, Britain 78
R Deron Williams scores 19 in his first start and Carmelo Anthony scores 19 in his first game off the bench.
• A 10-0 run to end the first quarter and an 8-0 run late in the second help put the game away for Team USA, which leads by as many as 47 points.
• Chicago Bulls All-Star Luol Deng scores a game-high 25 points for Britain.
P Team USA vs. Argentina at Barcelona, Sunday, 10 p.m.
TV • ESPN2