Priscilla Mullins was born probably in Dorking, Surrey, England, to William and Alice Mullins. She, her parents, and her brother Joseph all came on the Mayflower to Plymouth in 1620. Her entire family, herself excepted, died the first winter. She was shortly thereafter, in 1622 or 1623, married to John Alden, the Mayflower's cooper, who had decided to remain at Plymouth rather than return to England with the ship. John and Priscilla lived in Plymouth until the late 1630s, when they helped found the neighboring town of Duxbury.

John and Priscilla would go on to have ten or eleven children, and have an enormous number of descendants, including poet Henry Wadsworth Longfellow, Presidents John Adams and John Quincy Adams, and Vice President Dan Quayle.