The number of decks in play affects overall odds in blackjack by influencing the probabilities of drawing certain cards and changing the effectiveness of strategies like card counting. With fewer decks, there is a higher likelihood of certain card combinations and lower variability in outcomes, which can benefit players. Conversely, using multiple decks increases the odds against players by diluting the predictability of high and low cards remaining in play. This dilution can make it more difficult to count cards accurately and increases the house edge.