After the Galaxy won two of the teams' three regular-season games, the clubs will square off in the first match of the two-leg Western Conference semifinals.
The first game is Sunday at 6 p.m. at StubHub Center and the second is Thursday at Sandy, Utah.
The winner will be decided by the aggregate number of goals scored over the two games and will advance to a two-game conference final in hopes of qualifying for the MLS Cup championship game Dec. 7.
The aggregate-goals format means "if you prevail in the first 90 [minutes] it doesn't mean you're going to come out on top at 180-plus minutes," Galaxy Coach Bruce Arena said.
Real Salt Lake (16-10-8) and the Galaxy (15-11-8) finished the regular season in second and third place in the conference, respectively.
The teams agreed that the Galaxy's regular-season record against Real Salt Lake this year doesn't mean much in the postseason.
"It makes them the favorite" going in but the playoffs are "a completely new and fresh opportunity," Real Salt Lake Coach Jason Kreis said.
Still, Kreis acknowledged that the Galaxy's up-front offense is formidable.
Keane had 16 goals and 11 assists in the regular season, during which injuries and international duties with Ireland's national team limited him to 23 MLS games.
Donovan had 10 goals and nine assists in 22 games. The Galaxy's all-time leading scorer started late this season after a self-imposed sabbatical and spent time away with the U.S. national team.
The Galaxy "had a very difficult time this year getting our whole club together for any extended period of time," Arena said. "As of late, we've been able to do that with a little more consistency."
Arena added that goalkeeper Jaime Penedo also "has given us more consistency in the goal."
Real Salt Lake is led by forward Alvaro Saborio, who had a team-high 12 goals even though the Costa Rican was limited to 16 games, mostly because of injuries.
"Saborio is an excellent goal scorer for them up front," Arena said. "Nick Rimando has been an outstanding goalkeeper for them this season as he has been for the last five, six, seven years. It's a team that is very talented."
Real Salt Lake defeated the Galaxy on penalty kicks, 5-4, to win the MLS Cup in 2009. Two years later, the Galaxy defeated Real Salt Lake in the conference championship game, 3-1, en route to the league title.
As for Real Salt Lake this season, Donovan said, "You could argue they're as talented as any team in the league."
But in the playoffs, Donovan said, "it's more physical, it's more intense, and everything gets turned up a little bit. If we do that, we're a very hard team to beat."