Bungled handovers had denied the Americans gold at the last three Games but there were to be no mistakes on a balmy London night as the Americans added the Olympic crown to the world title they won last year.
Tianna Madison, Allyson Felix, Bianca Knight and Carmelita Jeter functioned like a well-oiled machine in overdrive to win comfortably and beat the world mark of 41.37 set by East Germany in 1985.
The Jamaican team, led off by 100 metres individual champion Shelly-Ann Fraser-Pryce, won silver in 41.41 seconds and the bronze went to Ukraine in 42.04 seconds, both countries setting national records in the process.
Jeter, the second fastest woman of all time over 100 metres, took the baton from Knight with a three-metre lead over the Jamaicans and extended it to five as she powered towards the line to claim her first Olympic gold.
The 32-year-old, runner-up in the 100 and bronze medallist in the 200, had time to look across and point at the trackside scoreboard as she crossed the line, giving a loud yell as she realised the record had fallen.
"I knew that we were moving, I knew we were running very well and I was so excited," she told reporters.
"It feels great. Everyone ran a credible leg and we were able to get the stick around, and we got the gold medal and the world record."
Silke Gladisch-Moeller, Sabine Rieger, Ingrid Auerswald-Lange and Marlies Goehr had set the old mark in Canberra and, although discredited to some by evidence of systematic doping in East Germany, it stood for more than a quarter of a century.
Felix, who ended her quest for an individual gold by winning the 200m in London, said the American team had been bursting with confidence ahead of the race.
"It is a relief, it is a joy. it is everything," she said. "It is the most comfortable that I have seen this team. We were laughing, we were smiling ... we have never been like that.
"I think it was a combination of practice and we were comfortable with each other. Then just the speed. Everyone was having fabulous years."
Veronica Campbell-Brown ran the third leg for Jamaica between Sherone Simpson and Kerron Stewart to clinch her seventh Olympic medal.
"I am happy for the U.S. girls," she said. "They broke the record, that is good. I feel good as a woman, I feel females don't get as much respect as their male counterparts.
"We need to get more records. It was an excellent run by the USA ... the result was phenomenal."
Olesya Povh, Hrystyna Stuy, Mariya Ryemyen and Elizaveta Bryzgina combined to finish third for Ukraine and claim bronze.
"We felt really strong out there," said Povh. "We were willing ourselves to win. Bronze is great, but of course we wanted to hear our national anthem."
- Allyson Felix