The two new franchises in MLS, Orlando City and New York City, will face off in the first round of the 2015 season.
MLS unveiled its schedule for the new campaign on Wednesday, featuring an expanded post-season involving 12 teams.
The year's first match will see champions LA Galaxy, who confirmed the signing of Steven Gerrard earlier in the day, host Chicago Fire on March 6.
Gerrard will not be available for that contest as he is scheduled to link up with his new team-mates in July.
New York are set to welcome another high-profile England international, Frank Lampard, to their roster in the same month.
However, two star names are on course to feature in New York's opening match in Orlando on March 8, with ex-Spain striker David Villa poised to come up against former Brazilian Kaka, a former World Player of the Year.
For the first time in MLS history, the final day of the regular season will see matches in each conference played simultaneously as the qualifiers for the play-offs are determined.
Every team will play 34 games, with six sides from each of the Eastern and Western Conferences earning play-off berths.
The season is set to end on either the weekend of December 5-6 or 12-13.