Twenty-eight former Appalachian League players were selected in the 2025 MLB Draft, which took place July 13-14 in Atlanta. The Boston Red Sox selected Marcus Phillips (ELZ '24) with the No. 33 overall pick, the highest picked Appy player this year. The River Riders led all Appy teams with seven selections in the 20-round draft.

Coming on in relief for the Tampa Bay Rays on June 21, 2025, right-hander Paul Gervase joined Jordan Leasure as the second Appy League alum to debut in the Majors. Gervase played for the Bristol State Liners in 2022 and was drafted by the Mets that year in the 12th round, joining the Rays organization in a deadline deal in 2024.

Nine former and current Appalachian League players accepted invitations to participate in the 2025 MLB Draft Combine, which took place at Chase Field in Arizona on June 17-21. Those players had the opportunity to take part in drills and show off their skills in front of MLB Club personnel.

Former Appalachian League Manager Kevin Mahoney was named an assistant coach on the New York Mets Major League staff ahead of the 2025 MLB season.

In 2024, right-handed reliever Jordan Leasure made the Chicago White Sox's Opening Day roster, becoming the first Appalachian League player to reach the Major Leagues since the league rebranded as a summer collegiate league in 2021. The 2021 Elizabethton River Rider has recorded multiple saves in back-to-back seasons with the White Sox.