Honolulu Little League of Honolulu, Hawaii, defeated Pabao Little League of Willemstad, Curaçao, in the championship game by a 13–3 score; the game ended in four innings due to the run rule.

This is also the first year of an annual rotational schedule involving the Caribbean and Latin America Regions whereby two of the three champions from Cuba, Panama, and Puerto Rico qualify directly while the third may still qualify through their normal regional tournament.

On August 22, 2021, it was announced that the fifth MLB Little League Classic would feature the Baltimore Orioles and the Boston Red Sox.

[7] The matchup was rescheduled from the 2020 MLB season when events were canceled due to the COVID-19 pandemic.

The game was played on August 21, 2022, at Muncy Bank Ballpark at Historic Bowman Field, and won by the Orioles, 5–3.