Football instituted its first half-the-distance penalty in 1889 for intentionally tackling below the knees, butting, tripping, and throttling (choking). Teams guilty of those offenses were penalized 25 yards. However, if the 25-yard penalty would take the ball over the goal line, they limited the penalty to half the distance.
The specifics changed occasionally, but the unsportsmanlike penalties had safety implications, so they were later deemed worthy of disqualifying the player from the game and penalizing his team half the distance.
College football's half-the-distance penalty remained in place until 1947, when they limited the penalty distance to fifteen yards because officials had become reluctant to call it.
Between the 1890s and 1946, however, some long penalties were assessed against teams. The longest I located came in 1901 when Northwestern had the ball on Minnesota's 8-yard line, and one of their players struck an opponent before the snap. Since the football field was 110 yards long in those days, the referee walked off a 51-yard penalty, taking the ball past the midfield stripe to Northwestern's 51-yard line.
The 1906 season saw Vanderbilt receive a 32-yard penalty, and Penn State watched 30 yards worth of gains disappear, but the 1912 shortening of the field to 100 yards meant penalties longer than 50 yards were no longer possible. Among the new longest can when Pittsburgh Pirates back Tony Holm stiff-armed an opponent's face at the 2-yard line, earning a 49-yard penalty in 1933.
The NFL limited roughness penalties to 15 yards soon after, and the colleges followed suit in 1947.
While half-the-distance penalties topped out at 49 yards, defensive pass interference is a spot foul in the NFL. That rule allowed Detroit Lions cornerback Nevin Lawson to incur a 66-yard penalty while playing the Packers in 2015. Lawson's penalty remains the longest I know about, but if there are examples of longer penalties, feel free to chime in below.
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Holy Snikeys! Those are some big yardage penalties! Great work Mr Brown. The research was very well done as usual.