Has an NFL game ever ended 21-6?
Yes. NFL has seen a final score of 21-6 21 times. It first happened on November 22, 1924, when Frankford Yellow Jackets beat Milwaukee Badgers, and most recently on September 7, 2025, when Washington Commanders beat New York Giants.
That makes 21-6 the 241st most common final score out of 1,095 that have ever occurred in NFL. One point away, 22-6 has happened 7 times and 21-7 has happened 85 times.