The 2008 U.S. Open Cup marked the first time that a pair of USL-1 teams advanced out of the quarterfinals for the second consecutive year.

In 2007, when the Seattle Sounders (USL-1) defeated the Colorado Rapids (MLS) 5-0, it was the worst loss suffered by an MLS team in the U.S. Open Cup.

In 2007, the USL First Division had three teams in the quarterfinals (Carolina, Charleston, Seattle), the most ever. That same year, only three MLS teams advanced to the quarterfinal round, the fewest ever. For the first time ever, two USL-2 teams (Richmond Kickers, Harrisburg City Islanders) made the round of eight in the same year.

The Carolina RailHawks and the Seattle Sounders won their quarterfinal matches in 2007, marking only the second time that two USL First Division teams had done that in the same year. In 1999, the Charleston Battery and the Rochester Raging Rhinos both made the semifinals, with Rochester eventually winning the tournament.

The USL First Division has been represented in the quarterfinals by at least one team in all but two tournaments (2000, 2006).