The Americans clocked 3 minutes, 52.05 seconds, slicing 0.14 off the previous mark set by China at the 2009 world championships at the height of the high-tech bodysuit era.
Missy Franklin swam the leadoff backstroke leg, Rebecca Soni did the breaststroke, Dana Vollmer competed in butterfly and Allison Schmitt had the anchor leg in freestyle.
The 17-year-old Franklin, who starts her senior year in high school this fall, finished the meet with four golds and a bronze, while Schmitt leaves with three golds, a silver and a bronze.
Donahue, who swam in the butterfly leg of the preliminary heats, helped guide the U.S. to the finals by turning in a fourth-place finish in the heats of the event on Friday, posting a time of 58.05 seconds.
Australia touched in 3:54.02 to take the silver medal and Japan finished in 3:55.73 to take bronze.