Aided by teammates Ryan Lochte, Ricky Berens and Peter Vanderkaay, the US led the entire race, winning in 6 minutes, 58.56 seconds and beating the previous record set by the Americans at last year's world championships in Australia.
The Russian team took silver with a time of 7:07.70 while Australia earned with 7:04.98.
|Phelp's gold haul
Athens 2004: six gold medals
400m individual medley
4x100m free relay
4x200m free relay
Earlier Phelps powered to victory in Wednesday's 200-metre butterfly, breaking the world record in the process with a time of 1 minute 52.03 seconds.
Hungary's Laszlo Cseh was second in 1:52.70, while Japan's Takeshi Matsuda took the bronze with a time of 1:52.97.
Wu Peng, who carried host China's hopes for a medal in the event, finished fourth.
It was a different tale however in the women's 200m freestyle with China's Pang Jiaying scoring an unexpected bronze behind winner Federica Pellegrini of Italy.
"I didn't expect this medal, my coach told me that even eighth place would be okay," said Pang, who hit the fingerboard more than two seconds ahead of her previous personal best.
|Phelps is targetting a record eight golds in Beijing [GALLO/GETTY]
Phelps' five events so far in Beijing have seen him shatter world records every time.
His 11 Olympic golds overall surpasses such Olympic icons as Paavo Nurmi, Carl Lewis, Mark Spitz and Larysa Latynina, who all won nine golds in their careers.
Phelps, who won six golds in Athens in 2004, is targeting a haul of eight gold medals in Beijing, aiming to break Spitz's record of seven golds in a single games.
Beijing's spectacular Water Cube venue saw more records tumble on Wednesday as Australia's Eamon Sullivan reclaimed the world record in the 100-metre freestyle semi-finals, about two minutes after Frenchman Alain Bernard took it from him.
Pellegrini's win in the women's 200m freestyle also set a new world record time of 1:54.82.
Wdednesday's victory makes Pellegrini, who won silver in Athens in 2004, Italy's first-ever female Olympic swimming champion.