In the National League, the San Francisco Giants and Cincinnati Reds returned for the second time in three years, the St. Louis Cardinals made their second straight appearance, the Washington Nationals made their first postseason appearance since 1981 (when they were originally the Montreal Expos), and the Atlanta Braves returned for the second time in three years.

The Orioles defeated the Rangers in the inaugural AL Wild Card game by a 5–1 score to return to the ALDS for the first time since 1997.

Both teams would meet again in the ALDS in the 2023 postseason, which would be won by the Rangers en route to a World Series title.

The Cardinals defeated the Braves 6–3 in the inaugural Wild Card Game to advance to the NLDS for the second year in a row.

Game 4 was another long extra-inning affair that lasted thirteen innings — the game remained scoreless for six innings after the bottom of the sixth, until Manny Machado helped the Orioles even the series by scoring on an RBI double from J. J. Hardy.

Despite blowing a 2–0 series lead, the Tigers held on in Game 5 thanks to a stellar pitching performance by Justin Verlander, and advanced to the ALCS for the second year in a row.

The Cardinals rallied late in Game 5 to upset the MLB-best Nationals and advance to the NLCS for the second year in a row.

The Cardinals set the record for the largest deficit a team overcame to win a winner-take-all game at six runs.

With the win, the Cardinals became the first fifth-seeded team to knock off a number one seed in the Division Series.

Both teams would meet again in the 2019 NLCS, which was won by the Nationals in a sweep en route to a World Series title.

The Giants overcame a 2–0 series deficit to defeat the Reds in five games and advance to the NLCS for the second time in three years.

Then in Game 5, the Giants jumped out to a 6–0 lead, and fended off a late comeback by the Reds to return to the NLCS.

Barry Zito pitched eight shutout innings as the Giants won 5–0 to send the series back to San Francisco.

The Tigers were considered as the favorite to win the title even though the Giants had the better record and home-field advantage.

[53] Despite having Triple Crown winner Miguel Cabrera, and the top two pitchers in the American League in Justin Verlander and Max Scherzer, the heavily-favored Tigers were shockingly swept by the Giants, who won their second title in three years and seventh overall.

[54] The Giants chased Verlander from the mound in a blowout victory in Game 1 which included Pablo Sandoval hitting three home runs.

The Tigers finally took their first lead of the series in Game 4, but it would not hold, and the Giants won the title in extra innings.

The Giants would return to the World Series in 2014 to face another AL Central team in the Kansas City Royals, who they defeated in seven games.

To date, this is the last appearance by a team from Detroit in the championship round in either one of the four major North American sports leagues.

The Tigers failed to return to the World Series the next year, losing to the Boston Red Sox in six games in the 2013 ALCS.

Under the original contract, TBS was awarded all Division Series games, with sister network TNT used as an overflow channel.