To calculate the probability of winning a lottery, divide the number of favorable outcomes (specific combinations that would result in a win) by the total possible outcomes (all possible number combinations in the game). This requires determining the total number of ways numbers can be selected, usually using combinatorics. For instance, in a lottery where you pick 6 numbers from a pool of 49, you would calculate the total combinations possible and find the ratio of winning combinations to this total. The result is the probability of winning.