In Professor Pac-Man, the players (or "pupils", as the game calls them) must answer multiple-choice questions by using the three Answer Buttons on the cabinet's control panel to answer either "A", "B", or "C"; unusually for an arcade game, the first player's Answer Buttons are on the right side of the panel (as is the game's 1-Player Start Button), while the second player's Answer Buttons and the game's 2-Player Start Button are on the left side of the panel.
In a one-player game, Professor Pac-Man challenges the player to answer the questions he asks correctly and quickly, in order to get the highest score; the player is given two chances to answer each question, but if they either fail to answer one before its timer (which is the original Pac-Man eating a row of pellets beneath Professor Pac-Man's desk) runs out, or answers it incorrectly on their first attempt, they will lose a fruit (the game's equivalent of lives, which also serve as a difficulty indicator). If time still remains on the question, the player can try to answer it again - however, if the timer runs out before they have the chance to do so, they will not lose another fruit (but if they do have enough time to try and answer it again, and are still incorrect, they will lose another fruit). The player may therefore use this to their advantage by not trying to answer a question for a second time if they are not entirely sure of its answer as they will not lose another fruit if they do not try, but they will lose one for a second attempt which also turns out to be incorrect; after the player has answered a certain amount of questions correctly in succession, they will be asked a bonus question (which they are only given one chance to answer) and if they answer it correctly, they will receive twice the usual point value, an additional fruit and an advancement to the next difficulty level (but if they answer it incorrectly, they will again not lose a fruit). After every thirtieth question, the number of consecutive questions that the player must answer correctly to receive a bonus question will be increased by two - and after every ninety-ninth question the number on Professor Pac-Man's desk will roll over to 1 and the game will continue. Once the player has inevitably lost their last fruit, their game will end; once they have entered their initials on the game's high-score table if their score was high enough, a silhouetted Professor Pac-Man will wave goodbye as the sun sets in the background.
In a two-player game, both players compete against each other to see which of them can answer each question correctly first; the player who manages to do this will receive the points for the question (but if either player answers a question incorrectly, they will lose a fruit, and the other player must try to answer it correctly in the time remaining). If they either fail to answer the question before the timer runs out or answer it incorrectly, they will also lose a fruit - and once either player inevitably loses their last fruit, the game will end for them, and the other player will continue as if it was a one-player game (that is, they will have two chances to answer each question). Once the remaining player also inevitably loses their last fruit, the game will end for them as well; once either (or both) of the players have entered their initials on the game's high-score table if either (or both) of their scores were high enough (as it is possible for only one score to be high enough), the silhouetted Professor Pac-Man will again wave goodbye as the sun sets in the background.