The National League will adopt the designated hitter full-time, a draft lottery will be implemented, the postseason will expand from ten teams to twelve, and advertising patches will appear on player uniforms and helmets for the first time.

[18] To replace Long, the Nationals announced the hiring of veteran hitting coach Darnell Coles, most recently of the Arizona Diamondbacks, on October 18, 2021.

[24] Organizational stalwart Spin Williams was joined by former Mets bench coach Dave Jauss as senior advisor to Watson in his new player development role.

[18] Catcher Alex Avila, left-handed pitcher Luis Avilán, first baseman Ryan Zimmerman, infielders Alcides Escobar and Jordy Mercer, and outfielder Gerardo Parra were set to become unrestricted free agents following the 2021 season.

[29] Avilán signed a new minor league deal in November to remain with the Nationals as he continued to rehab from Tommy John surgery.

[36] The Nationals entered the offseason with ten players expected to be eligible for salary arbitration: right-handed pitchers Erick Fedde, Ryne Harper, Tanner Rainey, Joe Ross, Wander Suero, and Austin Voth, first baseman Josh Bell, and outfielders Víctor Robles, Juan Soto, and Andrew Stevenson.

[56] The lockout was in effect for 99 days, delaying the start of spring training and forcing some games in the regular season to be rescheduled, before owners voted unanimously to lift it after a new collective bargaining agreement was agreed to March 10, 2022.

[57] Following the lockout, the Nationals signed infielder Ehire Adrianza and right-handed reliever Steve Cishek to major league deals announced March 14, 2022.

[59] Nelson Cruz signed a one-year deal with the Nationals that was announced the following day, filling Washington's need at the new designated hitter lineup spot.

[60] With an open roster spot due to third baseman Carter Kieboom spraining his ulnar collateral ligament of the elbow and landing on the 60-day injured list, the Nationals claimed former first-round pick Hunter Harvey, a right-handed pitcher, off waivers from the San Francisco Giants on March 21.

[62] Non-roster participants in major league spring training for the Nationals included right-handed pitchers Víctor Arano, Cade Cavalli, Carl Edwards Jr., Jace Fry, Reed Garrett, Erasmo Ramírez, Jefry Rodríguez, Jackson Rutledge, Aaron Sanchez, Aníbal Sánchez, and Jordan Weems; left-handed pitchers Luis Avilán, Alberto Baldonado, and Matt Cronin; catchers Taylor Gushue, Chris Herrmann, Drew Millas, and Israel Pineda; infielders Jackson Cluff, Maikel Franco, Jake Noll, Adrián Sánchez, Dee Strange-Gordon, Richard Ureña, and Andrew Young; and outfielder Gerardo Parra.

[63] Right-handed reliever Tyler Clippard, who pitched with the Nationals for seven years through the 2014 season, was a late addition to the list of non-roster invitees, signing a minor league deal with Washington announced March 26.

Carter Kieboom, expected to contend for an everyday role again as Washington's third baseman, landed on the 60-day injured list after being diagnosed with a flexor mass strain and partially torn UCL in his right arm.

[67] Reliever Will Harris, in the final year of an injury-plagued three-year contract with Washington, appeared in just one game before being sidelined with lingering issues from his 2021 thoracic outlet surgery.

[70] Stevenson's roster spot went to Aníbal Sánchez, who was initially a non-roster invitee in his return to the Nationals organization after previously pitching for Washington in the 2019 and 2020 seasons.

[71] The Nationals also gave Arano, Franco, and Strange-Gordon spots on the Opening Day roster, as well as promoting prospects Joan Adon and Lucius Fox after they impressed during spring training.