The knockout round begins in February and is headlined by a clash between MLS' CF Montreal and Liga MX's Santos Laguna. As the only round of 16 battle with representatives from the top two leagues in the confederation, plenty of eyes will be focused on the series that will feature the 2021 Clausura finalists Santos and Montreal, the winners of the 2021 Canadian Championship.
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Elsewhere, recent MLS Cup Champions New York City FC will face off against CCL debutants Santos de Guapiles from Costa Rica. The Costa Rican club earned a spot into the competition as one of the top quarterfinalists from the 2021 CONCACAF League.
This year's MLS Supporters' Shield winners New England Revolution are placed against 2021 CONCACAF Caribbean Club Championship winners Cavaly, the lone Haitian representatives that will also be making their CCL debut.
MLS Western Conference winners the Colorado Rapids will take on Guatemala's Comunicaciones, which recently defeated Motagua for the 2021 CONCACAF League title on Tuesday night. Fresh off their loss, Motagua will take on theSeattle Soundersin the CCL round of 16.
The Sounders booked their place into the CCL after the absence of a U.S. Open Cup tournament this year. With the tournament cancelled last year due to the COVID-19 pandemic, U.S. Soccer announced in September that the Open Cup slot for the CCL would be given to the "highest-ranked U.S. based Division I club (based on 2021 MLS regular season record) not already qualified."
In other matchups, 2020 Apertura champions Leon will face off against CONCACAF League semifinalists Guastatoya from Guatemala, while 2020 Apertura finalists Pumas will take on Costa Rica's CONCACAF League quarterfinalists Saprissa.
2021 Clausura winners Cruz Azul will square off against Canada's Hamilton Forge FC, the third team in 2022 that will be making their CCL debut. Hamilton Forge FC secured its spot for next year's competition as one of the CONCACAF League semifinalists.
MLS clubs and the rest of the confederation will look to end Liga MX's dominant run of 13 consecutive seasons with a CCL title, which stretches back to 16 consecutive campaigns when counting the "Champions' Cup" era.
NYCFC beats Portland Timbers on penalties to win first title
NYCFC is crowned MLS Cup champion for the first time after a 4-2 win on penalties vs. the Portland Timbers.
NYCFC wins first MLS Cup title in penalty shootout
NYCFC defeats the Portland Timbers on penalties to secure the first title in club history.