After becoming the best-selling game (Resetera) in April 2021, MLB: The Show 21 surpassed 4 million players on the calendar and became the second most profitable and successful game of the year. With the start of the Major League Baseball (MLB) season, the game's Metascore is 81 points and the introduction of a two-way player feature has become more and more popular.

According to NPD, MLB: The Show 21 sold 2 million copies on PlayStation, with The remaining 2 million copies coming from Xbox and GamePass. As the fastest-selling game in the series, the game became SONY's most profitable game of the year and one of the best baseball video games on the market.