[12][13][14] The Nationals also saw utility infielders Asdrúbal Cabrera and Brock Holt, relief pitcher Sean Doolittle, catcher Kurt Suzuki, and first baseman Ryan Zimmerman depart as unrestricted free agents.

[39] The Nationals also reached one-year deals with their three other arbitration-eligible players, first baseman Josh Bell, outfielder Juan Soto, and shortstop Trea Turner, on the January 15, 2021, deadline to exchange salary figures.

Other invitees included: pitchers Luis Avilán, Aaron Barrett, Bryan Bonnell, Tim Cate, Jacob Condra-Bogan, Matt Cronin, Tyler Dyson, Tyler Eppler, Paolo Espino, Javy Guerra, Cole Henry, Gabe Klobosits, T. J. McFarland, Todd Peterson, and Jefry Rodriguez; catchers Welington Castillo, Israel Pineda, Raudy Read, Jakson Reetz, and Blake Swihart; infielders Jackson Cluff, Drew Mendoza, Jordy Mercer, Hernán Pérez, Adrián Sanchez, and Brandon Snyder; and outfielders Gerardo Parra, Carlos Tocci, Yasmany Tomás, and Cody Wilson.

On March 27, the Nationals made their final major round of roster cuts, designating rookie infielder Jake Noll for assignment and purchasing the contracts of veteran utilitymen Jordy Mercer and Hernán Pérez.

The Nationals also brought up Luis García, Carter Kieboom, Yadiel Hernández, Tres Barrera, Sam Clay, Ryne Harper, and Kyle McGowin after previously optioning them to the minors during spring training.

[71] Wilson was returned to the Nationals' alternate training site on April 9, as infielder Jordy Mercer, catchers Alex Avila and Yan Gomes, and reliever Brad Hand were activated from the injured list.

[88] Although Rainey blew the save as St. Louis took a one-run lead in the seventh inning, the Nationals won 3–2 on a game-tying single by shortstop Trea Turner and a go-ahead bases-loaded walk by the catcher Gomes versus Cardinals reliever Giovanny Gallegos.

The Marlins drove in their free baserunner for the first run of the game, but the Nationals immediately answered back with a game-winning blast off the bat of Schwarber leading off the bottom of the tenth, driving in their own unearned runner and topping Miami 2–1.

[100] For the first time in 2021, on May 1, the Nationals won a third consecutive game, topping the division-rival Miami Marlins behind a strong seven innings from Patrick Corbin and big offensive performances from catcher Yan Gomes, who hit a two-run home run, and first baseman Josh Bell, who drove in four including via a bases-clearing double.

[103] Before the May 4 game, the Nationals designated utilityman Hernán Pérez for assignment and optioned reliever Kyle McGowin, clearing space on the roster to activate outfielder Juan Soto and setup man Will Harris.

[104] But the May 4 game went poorly, as 22-year-old Atlanta starter Huascar Ynoa effectively shut down the Nationals' offense, allowing just one unearned run over seven strong innings—as well as slugging a grand slam off struggling Washington reliever Tanner Rainey in the sixth inning.

[120] Optioned to make room on the active roster for Corbin, Espino wasn't down for long, being recalled alongside McGowin the next day when Fedde tested positive for COVID-19 and Rainey was also placed on the COVID-19-related injured list as an unvaccinated close contact.

Starting pitcher Stephen Strasburg was activated May 21, with McGowin once again optioned to Triple-A Rochester, and earned the win in that night's game by pitching into the sixth inning while allowing just a single hit, although he also walked four Orioles and only struck out one.

[129] The Nationals held on to win the suspended game 5–3 despite an unsteady performance by Hudson in the eighth inning, getting crucial insurance runs after recently recalled infielder Luis García delivered a pinch-hit triple in the sixth.

The visitors enjoyed another two-homer game by Schwarber, who hammered a leadoff home run into the second deck and then hit a three-run homer in the second inning off Marlins starter Cody Poteet, and a strong seven-inning performance from Ross.

[173] Coming off their best month in nearly two years, the Nationals immediately ran into an obstacle in July: the defending world champion Los Angeles Dodgers, who arrived in Washington, D.C., for a four-game series and summarily swept their hosts.

Mookie Betts singled in a pair of runs off Nationals reliever Austin Voth, pinning him with a blown save and giving the Dodgers the lead in the seventh inning, part of a nine-run outburst that put the game out of reach.

After a first-inning home run by the returning Turner, the Nationals squandered an early five-run lead, as the Padres answered back to tie the game off Washington starting pitcher Jon Lester in the fourth inning.

Right fielder Juan Soto opened the scoring with a three-run home run in the first inning off Padres starter Chris Paddack, setting the tone for a game in which neither San Diego's starting pitcher nor its bullpen could slow down the Nationals' offense.

Scherzer quickly got ahead with two strikes and tried to finish off the inning by enticing a swing and a miss on a 97 miles per hour (156 km/h) fastball below the knees; instead, Camarena swung and connected, pulling a grand slam home run into the stands beyond right field.

The Nationals' bats went quiet as they were held to one hit for the rest of the game, while Tommy Pham doubled in the game-tying run in the sixth inning and then scored on Trent Grisham's walk-off single off Clay in the ninth.

[232] A hit by Bell that kicked off the second base bag closed the deficit to a single run, but the Nationals could not level the game, and after scoring on the odd play, Soto reported pain in his left knee.

[234] The visitors appeared to be headed for their sixth straight loss on August 7, as despite a strong five-inning start from top prospect Gray, who struck out ten Braves[note 13] and allowed just one earned run, and effective work from the Nationals' bullpen, Charlie Morton led the Atlanta pitching staff in throwing eight shutout innings.

Kieboom homered in the ninth inning off reliever Hoby Milner, and back-to-back hits by Thomas and shortstop Alcides Escobar forced Brewers manager Craig Counsell to insert his closer, Josh Hader.

[274] With rosters expanding to 28 players, the Nationals activated veteran catcher Alex Avila from the injured list after nearly two months out of action, and they also selected the contract of 28-year-old journeyman left-handed reliever Alberto Baldonado from their Triple-A affiliate, the Rochester Red Wings.

[281] To start the second game of the doubleheader, the Nationals selected the contract of left-handed pitcher Josh Rogers from the Red Wings, placing reliever Kyle McGowin on the 60-day injured list—and thereby ending his season—after he was diagnosed with a sprained right ulnar collateral ligament of the elbow.

[note 17] On September 5, the Nationals placed Parra on the injured list with inflammation in his surgically repaired right knee, keeping Rogers on the active roster after he played as the "extra man" under doubleheader rules the previous day.

[297] The next night, playing in front of first responders and family members of United Airlines Flight 93 crash victims in honor of the 20th anniversary of the September 11, 2001, terror attacks that claimed lives in both Western Pennsylvania and the National Capital Region, the Pirates again rebounded from a deficit.

After Escobar tied the game with a cue shot into right field in the bottom of the eighth, Bell beat out a potential double play ball to bring home Thomas and put the Nationals back on top.

The Nationals tied the game in the eighth inning when right fielder Juan Soto ripped a pitch from Red Sox reliever Austin Davis to deep center field, just missing a grand slam but settling for a sacrifice fly.