Since the expanded format in 1997, a PDL team has failed to reach the third round only four times (1998, 2002, 2007, 2008). The recent struggles can be attributed to the fact that in 2007, the format was changed so that all non-MLS teams began the tournament in the first round, unlike previous tournaments where PDL teams were matched up with USASA or other PDL clubs.

The biggest rout in the third round during the Professional Era came in 2003, when the Virginia Beach Mariners defeated the Carolina Dynamo 5-0. Dante Washington and Roland Aguilera both scored twice for the Mariners.

The highest scoring Professional Era Open Cup game occurred in the third round on July 19, 2005 when the Richmond Kickers (USL-1) defeated the Ocean City Barons (PDL) 8-4. The game was played at Sports Backers Stadium in Richmond, VA, a week after the original match was re-scheduled due to bad weather. The Barons scored first in the 4th minute, but Richmond stormed back with four goals in less than 20 minutes. With the score 4-1, Ocean City scored a pair of goal on either side of halftime to cut the lead to one. At that point, the Barons manager made some offensive-minded substitutions and pushed for the equalizer, but at that point, the flood gates opened and Richmond scored four more in the second half, and the game would finish 8-4. The previous total goals record was shared by a pair of games. In 1995, the Seattle Sounders (A-League, now USL-1) defeated the Everett BigFoot (USISL Pro, now USL-2) 9-2 and in 1999 the San Diego Flash (A-League) cruised past the Arizona Sahuaros (D3 Pro, now USL-2) by the same score.

In 2007, a record five MLS teams were upset in the third round, with only three clubs advancing to the next round (a record low for MLS teams).

In 2007, two USL Second Division clubs (Richmond Kickers, Harrisburg City Islanders) won third round matches. It was the first time that two USL-2 teams advanced beyond round three in the same year. Prior to 2007, only one USL-2 club, the Wilmington Hammerheads, had ever advanced beyond the third round and they did it twice (2003, 2006).