Four patients received the jab at the Kaiser Permanente research facility in Seattle, Washington.
The vaccine cannot cause Covid-19 but contains a harmless genetic code copied from the virus that causes the disease.
Experts say it will still take many months to know if this vaccine, or others also in research, will work.
The first person to get the jab on Monday was a 43-year-old mother-of-two from Seattle.
Scientists around the world are fast-tracking research.
But the biotechnology company behind the work, Moderna Therapeutics, says the vaccine has been made using a tried and tested process.