Andy Reid of the Kansas City Chiefs and Mike McCarthy of the Green Bay Packers were selected to coach the teams due to their teams being the highest seeded teams from each conference to lose in the Divisional Round of 2015–16 NFL playoffs, which has been the convention since the 2010 Pro Bowl. On January 27, Mike McCarthy announced that he would not be coaching the Pro Bowl due to an illness and also announced that assistant head coach Winston Moss would take over head coaching duties. This was also the sixth consecutive year that the Pro Bowl took place prior to the Super Bowl. At the Pro Bowl Draft, the Chiefs' coaching staff was assigned to Team Rice, and the Packers' coaching staff was assigned to Team Irvin.
The game format was nearly the same for 2016 as it had been in 2015. The previous year's experimental rule of kicking the point after touchdown from the 15-yard line became a permanent rule. The goal posts remained at their normal 18-foot width in 2016, as compared to the narrower 14-foot width from the 2015 Pro Bowl.
Forty-three players were assigned to each team, down from 44 in 2015 (a regular game-day active roster has 46).
A two-minute warning was given in the first and third quarters (as well as in the second and fourth quarters), and the ball changed hands after each quarter.
The coin toss determined which team was awarded possession first. There were no kickoffs; the ball was placed on the 25-yard line at the start of each quarter and after scoring plays.
Defenses were now permitted to play cover two and press coverage. Prior to 2014, only man coverage was allowed, except for goal line situations.
Beginning at the two-minute mark of every quarter, if the offense did not gain at least one yard, the clock stopped as if the play were an incomplete pass.
The game clock started after an incomplete pass on the signal of the referee, except inside the last two minutes of the first half and the last five minutes of the second half.
A 35-second/25-second play clock was used instead of the usual 40-second/25-second clock.
The game clock did not stop on quarterback sacks outside the final two minutes of the game. Formerly, the clock stopped on these situations outside the final two minutes of the second and fourth quarters.