Rhode, a medallist in Atlanta, Sydney, Athens and Beijing, destroyed the field at the Royal Artillery Barracks, never looking remotely in danger under cloudy skies in south London.
China's Wei Ning won silver with Danka Bartekova of Slovakia taking bronze after a shoot-off. But the competition was a procession for Rhode -- who then warned her rivals she had no intention of retiring.
Rhode, 33, won golds in women's double trap in Atlanta in 1996 and in Athens in 2004, taking bronze in the event in Sydney in 2000.
She switched to skeet full-time when women's double trap was discontinued as an Olympic event after Athens, and grabbed silver in the discipline four years ago in Beijing.
"One got away but everyone misses every now and then," said a delighted Rhode.
"I know that I felt very comfortable in that final round and through the match and was really ready. I felt that I had done everything I could and there wasn't anything more and I was just going to let the chips lay where they may."
"It's just been an incredible journey and ultimately I couldn't be happier for bringing home the gold for the United States," she added.
Speaking about her American first, she said: "I don't think it's hit me yet. I'm sure later on tonight that the record and everything that represents (will hit me). Right now I'm just focusing on my second event... and hopefully we'll be looking at 2016. I'm not looking at this being my last Olympics."
"I can go on for a very long time," added Rhode. "That's the beauty of shooting. It's something you can do. It's not a flash-in-the-pan type thing. I definitely don't see any end in sight."
After a bright start to the day, storms swept across the temporary venue but the rain held off for the final, where Rhode finished with 99 hits out of 100 of the fast-moving clay pigeon targets.
Wei was a distant second with 91 hits, while Bartekova was involved in a shoot-off for bronze after she finished level on 90 hits with Russia's Marina Belikova.
Rhode came top in the qualifying competition, hitting 74 targets out of 75 to notch a new Olympic record.
Skeet requires competitors to hit a clay target moving away from them. The top six shooters from the qualification go into the final, where they fire a further 25 targets, with the scores added to their qualifying tally.
Rhode's build-up to the London Games was hit when flight problems forced her to miss her team's training camp in Denmark, and when her four-month-old puppy ate her plane ticket.
© Copyright AFP Agence France-Presse GmbH - All rights reserved. This material may not be published, broadcast, rewritten or distributed. All reproduction or redistribution is expressly forbidden without the prior written agreement of AFP.