Coughlin touched in 2 minutes, 9.77 seconds, lowering the mark of 2:10.05 set by Katie Hoff.
"I've only done this event twice in the last five years," Coughlin said. "It was obviously a good swim. I didn't have anything else to swim today. It was the first on the schedule, that's why I swam it."
Julia Smit was second in 2:13.22 at the meet on the Southern California campus.
Coughlin is aiming at making her second Olympic team. She won five medals at the 2004 Athens Games, including gold in the 100 backstroke and the 800 freestyle relay.
Jessica Hardy won the 50 free in her home pool, finishing in 24.98 seconds. Later, she added the 100 breaststroke title.
Hardy, seeking to make her first Olympic team at 21, won in 1:07.04, ahead of Olympian Tara Kirk. Rebecca Soni was third.
Jason Lezak, at 32 the oldest man in the field by four years, won the men's 50 free in 22.34. Ben Wildman-Tobriner, the defending world champion, was second in 22.36.
Savannah King of Canada won the 400 freestyle in 4:13.57, ahead of training partner Tanya Hunks, who touched in 4:13.96.
Tamas Kerekjarto of Hungary, who trains at USC, won the 200 IM in 2:01.76, ahead of training partner Vanni Mangoni. Brian Johns of Canada was third.