Each team played 34 matches during the regular season from April to early November, primarily against intra-conference opponents with the schedule varying based on conference to minimize travel due to the COVID-19 pandemic.

[10] During the pandemic-shortened 2020 season, the club finished as champions of the MLS is Back Tournament in Florida and third in the Western Conference,[11] but were eliminated in the first round of the playoffs by FC Dallas in a penalty shootout.

[12] During the 2020–21 offseason, the Timbers traded away two of their left backs, Jorge Villafaña and Marco Farfan, and acquired wingbacks Claudio Bravo and Josecarlos Van Rankin as replacements.

[20][7] Following an early June break in league play for the 2021 CONCACAF Gold Cup, the Timbers were able to earn a win against Sporting Kansas City and a comeback draw with the Houston Dynamo to reach fifth in the conference.

[23] During the summer transfer window, Portland signed midfielders George Fochive as a replacement for Polo and Santiago Moreno as a Young Designated Player;[24][25] the club also traded Jeremy Ebobisse to the San Jose Earthquakes, a move that opened a starting role for striker Felipe Mora.

[26] The Timbers re-entered playoff contention in early August by tying San Jose Earthquakes and defeating Real Salt Lake to begin a three-match homestand, which finished with a 6–2 loss to rivals Seattle Sounders FC.

[29][30] After dropping to ninth place in the west, the Timbers closed out August with a 2–0 win against the Sounders in the middle of five consecutive road matches, but lost midfielder Eryk Williamson for the rest of the season due to an ACL tear.

[33] The Timbers clinched a playoff berth in their last match of October, winning 2–0 against San Jose, and finished the season by defeating Real Salt Lake and Austin FC.

[34][35] Portland finished the 2021 regular season with 55 points and 17 wins, setting a club record for their time in MLS, and earned the fourth playoffs seed in the Western Conference.

Franco Fragapane scored the opening goal for Minnesota with a sliding shot in the 11th minute, but Larrys Mabiala's header shortly before half-time tied the match.

[37] Portland advanced to the Conference Semifinals, hosted by the top-seeded Colorado Rapids on Thanksgiving, and won 1–0 with a Mabiala goal in the 90th minute amid a scramble in the penalty area.

[41][42] The 2020 season, their first under new manager Ronny Deila, ended with a fifth-place finish in the Eastern Conference and a first round exit from the playoffs in a penalty shootout against Orlando City SC.

[50] The team were then without goalkeeper Sean Johnson and James Sands during the Gold Cup, as well as new signing Talles Magno due to an injury, as they entered a stretch of 10 matches in 36 days beginning in mid-July.

[52] NYCFC finished fourth in the East and began their 2021 playoffs run by defeating Atlanta United FC 2–0 in the first round at home, scoring twice within four minutes in the second half.

[53] NYCFC advanced to play Supporters' Shield champions New England Revolution in the Conference Semifinals at Gillette Stadium, where they drew 2–2 after extra time despite leading goalscorer Valentín Castellanos being sent off by earning a second yellow card.

[54] Their Eastern Conference Final opponents, the Philadelphia Union, were unable to field a full roster due to the absence of 11 players—including several starters—required to quarantine under the league's COVID protocols.

The match was declared sold out within 20 minutes of the first release, with only general admission seating left available, amid an Amazon Web Services outage that affected SeatGeek, the league's ticket vendor.

[69] The ABC broadcast featured Jon Champion as the play-by-play announcer and Taylor Twellman as color commentator, along with Sam Borden as sideline reporter and Mark Clattenburg as rules analyst.

[80] The Timbers equalized in the fourth minute of stoppage time, the latest regulation-time goal in MLS Cup history, as Felipe Mora struck from within the penalty area off a rebounded ball.