The return of the Browns increased the number of teams to 31, the first time the league had played with an odd number of clubs since 1966. As a result, the NFL was forced to give at least one team a bye each week; Previously, barring extreme circumstances, a club never received a bye during the first two weeks or last seven weeks of the season. Under a new system, for ten weeks of the season (Week #1 to Week #2, and Week #10 to Week #17), one team was scheduled a bye; for seven weeks of the season (Week #3 to Week #9), three teams sat out. This format would continue for the next two seasons until the Houston Texans joined the NFL in 2002 and returned the league to an even number of teams.
The start of the 1999 NFL Season was pushed back one week and started the weekend after Labor Day, a change from the previous seasons. Due to the Y2K concerns, the NFL did not want to hold the opening round of the playoffs on Saturday January 1, 2000, and did not want teams traveling on that day. Week 17 games were held on January 2, 2000, and the opening round of the playoff would be scheduled for January 8–9. The bye week before the Super Bowl was removed to accommodate the one-week adjustment. The start of the season after Labor Day would become a regular fixture for future seasons, beginning in 2001.
The final spot in the NFC playoffs came down to an exciting final day of the season. With both the Green Bay Packers and Carolina Panthers at 7–8 and tied for the last spot in the playoffs with the Dallas Cowboys, and tied in other tiebreakers, the tie between them would be determined by best net point differential in conference games. Both the Packers and Panthers were playing at 1:00 PM Eastern on January 2, and both teams tried to outscore the other. The Packers beat the Arizona Cardinals 49–24, and the Panthers beat the New Orleans Saints 45–13. The Packers finished ahead of the Panthers by 11 points, but Dallas defeated the New York Giants later that night to claim the final playoff spot.
The St. Louis Rams, who had a losing record for each of the past nine seasons, surprised the entire league by defeating the Tennessee Titans in Super Bowl XXXIV.
Clipping is now illegal around the line of scrimmage just as it is on the rest of the field.
A new instant replay system (different from the one used from 1986 to 1991) is adopted to aid officiating. The system mirrors a method used by the defunct USFL in 1985:
In each game, each team has two challenges that will start a review. Each challenge will require the use of a team's timeout. If the challenge is successful, the timeout is restored.
Inside of two minutes of each half, and during all overtime periods, all reviews will be initiated by a Replay Assistant. The Replay Assistant has an unlimited number of reviews, regardless of how many timeouts each team has left. And no timeout will be charged for any review by the Replay Assistant.
All replay reviews will be conducted by the referee on a field-level monitor. A decision will be reversed only when there is indisputable visual evidence to overturn the call. The referee has 90 seconds to review the play.
The officials will be notified of a replay request or challenge via a specialized electronic pager with a vibrating alert. Each head coach would also have a red flag to use as a backup to get the attention of the officials to challenge a play.
The replay system will only cover the following situations:
Runner/receiver out of bounds
Recovery of a loose ball in or out of bounds
Touching of a forward pass, either by an ineligible receiver or a defensive player
Quarterback pass or fumble
Illegal forward pass
Forward or backward pass
Runner ruled not down by contact
Forward progress in regard to a first down
Touching of a kick
Too many men on the field
The league also added the following then-minor rule change that became significant in the playoffs a few years later:
When a Team A player is holding the ball to pass it forward, any intentional forward movement of his hand starts a forward pass, even if the player loses possession of the ball as he is attempting to tuck it back toward his body. Also, if the player has tucked the ball into his body and then loses possession, it is a fumble.
This new interpretation of a forward pass would later be commonly known as the "Tuck Rule".