Edward IV's marriage to Elizabeth Woodville took place secretly (with only the bride's mother and two ladies in attendance) on 1 May 1464, at her family home in Northamptonshire.

At around the time of Edward's secret marriage, Warwick was negotiating an alliance with France in an effort to thwart a similar arrangement being made by his sworn enemy Margaret of Anjou, wife of the deposed Henry VI. The plan was that Edward should marry a French princess. When the marriage to Elizabeth became public, its concealment was the cause of considerable rancour on Warwick's part. Later, when Elizabeth's relatives, especially her brother, Anthony Woodville, 2nd Earl Rivers, began to be favoured over him, he turned against Edward and eventually changed sides. In fact, he and Margaret of Anjou formed an alliance of their own to restore Henry to the throne and Warwick's daughter Anne married Margaret's son Edward.

Elizabeth was crowned Queen on Ascension Day, 26 May 1465. There was an infamous incident at her coronation which was not attended by Edward IV (kings traditionally did not attend their consorts' coronations) in which her mother's Luxembourg kinsmen landed in a ship at Ship's Green and arrived at Westminster Abbey carrying shields painted with the figure of Melusine, a "water-witch" (actually a medieval version of the old pagan goddess) described variously as a mermaid or possibly as a female figure depicted as a snake from the waist down, but with the face clearly that of the young queen. This immediately caused whispers of witchcraft to circulate throughout the Abbey, as it was indeed the intention of the Luxembourgers to suggest an accusation of witchcraft thereby. Elizabeth's brother Anthony came to her rescue, driving the Luxembourg kinsmen forth from the Abbey all the way to Ship's Green where he would not allow them to embark and depart until he had answered this charge of witchcraft in single combat with every one of them and scratched every Melusine shield. (This "infamous incident" appears to be a modern invention. It is not recorded in any of Elizabeth Woodville's modern biographies, including the relatively hostile one by David MacGibbon, or in any contemporary chronicle. The charge of witchcraft was later laid against the Duchess of Bedford in 1469, some considerable time after the Coronation, by a follower of the Earl of Warwick, and she was acquitted the following year. Although Richard III in declaring Elizabeth's children by Edward IV to be illegitimate accused Elizabeth Woodville of having procured her marriage through witchcraft, he never brought her to trial on witchcraft charges or otherwise proved their veracity, and the 1484 Act of Parliament that contains the witchcraft charge, Titulus Regius, gives no pertinent details. The House of Luxembourg, however, is said to have claimed a mythical descent from Melusine, but there is no evidence that Elizabeth Woodville made use of this legend or that her beliefs were anything other than the conventional Christianity of her day.)

Nor was Warwick the only one who resented the way the queen's relatives scooped up favours and lucrative opportunities; in 1480, for example, when Elizabeth's obscure brother-in-law Sir Anthony Grey died (the second child of Lady Katherine Percy and Edmund Grey, Earl of Kent), he was interred in St Albans Abbey with a brass marker to rival the one for the abbey's greatest abbot.

That was nothing compared to the marriages the queen arranged for her family, the most outrageous being when her 20-year-old brother John Woodville| married Lady Katherine Neville, daughter of Ralph Neville, 1st Earl of Westmorland by Joan Beaufort, widow of John Mowbray, 2nd Duke of Norfolk and dowager Duchess of Norfolk. The wealthy Katherine had been widowed three times and was probably in her sixties.

The queen also married her sister, Catherine Woodville, to her 11-year-old ward Henry Stafford, 2nd Duke of Buckingham. Another sister, Mary Woodville, married William Herbert, 2nd Earl of Pembroke.

Elizabeth and Edward's marriage was to produce ten children, including two sons who were still living at the time of the King's sudden death in 1483. The elder, Edward, had been born in sanctuary at Westminster Abbey in 1470, during the period when his father was out of power and in exile following his overthrow by Warwick in favour of Henry VI — Edward later returned to England and Warwick was killed at the Battle of Barnet in 1471. Henry VI was later murdered.

Following Edward's death, Elizabeth now, briefly, became Queen Mother, but on 25 June 1483, her marriage was declared null and void by Parliament in the act Titulus Regius on the grounds that Edward had previously promised to marry Lady Eleanor Butler, which was considered a legally binding contract that rendered any other marriage contract invalid as bigamous. (It was said that Eleanor Butler had done the same thing Elizabeth Woodville did later: a widow who caught Edward's eye, she refused to give in to him until he promised to marry her.) This information came to the fore when a priest (believed to be Robert Stillington, Bishop of Bath and Wells), testified that he had carried out the ceremony.

On the basis of his evidence, all Elizabeth's children by Edward, including King Edward V, were declared illegitimate, and her brother-in-law, Richard III, was given the crown. Young Edward and his brother Richard, Duke of York, were kept in the Tower of London, where they had already been lodged to await the coronation. The exact fate of the so-called Princes in the Tower is unknown but both were dead in this or the next reign.

Elizabeth now lost the title of Queen Mother and was referred to as Dame Elizabeth Grey. She and her other children were in sanctuary again, fearing for their safety. This may have been to protect themselves against jealous courtiers who wanted revenge against the entire Woodville clan.

Scholars differ about why Queen Dowager Elizabeth spent her last five years living at Bermondsey Abbey. Among her modern biographers, David Baldwin believes that Henry VII forced her retreat from the Court, while Arlene Okerlund presents evidence that indicates she was planning a religious, contemplative life as early as July 1486. At the Abbey, Elizabeth was treated with all the respect due to a Queen Mother, lived a regal life, and received a pension of £400 and small gifts from the King. She did not attend her daughter's coronation, but was present at the birth of her second grandchild, Margaret, at Westminster Palace in November 1489. The Queen rarely visited her, although Elizabeth's younger daughter, Cecilia Welles, who had secretly married Viscount Welles, came to see her as often as she could.

Henry VII briefly contemplated marrying her off to King James III of Scotland, when James' wife, Queen Margaret, died in 1488. James was killed in battle later that year, rendering the plans of Henry VII moot.

Elizabeth died on 8 June 1492. With the exception of the Queen, who was awaiting the birth of her fourth child and Cecilia (Viscountess Welles), her daughters attended the funeral at Windsor Castle: Anne (the future Countess of Surrey), Catherine (the future Countess of Devon) and Bridget (a sister at Dartford Priory). Her will specified a simple funeral. Many ardent Yorkists, who considered themselves slighted by the ordinary and very simple burial of Edward IV's Queen on 12 June 1492, were not pleased. Elizabeth was laid to rest in the same chantry as her husband King Edward IV in St George's Chapel in Windsor Castle.

During her later years, Elizabeth Woodville had the satisfaction of knowing that her daughter was securely on the consort's throne. She lived to see the birth of two grandsons, Princes Arthur and Henry, the latter of whom would later become Henry VIII. Through her granddaughter, Queen Margaret of Scotland, Elizabeth became an ancestress of the Stuart, Hanover, and Windsor dynasties, whose descendants reign in England, Scotland and Wales today. Her great granddaughter and namesake Elizabeth I (the Virgin Queen) became arguably the greatest female monarch to sit on the English throne.