Nike hired Miami-based Crispin in April 2007 to handle its global running shoe account, as well as its Nike Plus and Nike ID website business. Its portion of the business is estimated at $50m (£25m).
The move came as a blow at the time to Wieden & Kennedy Portland, which had long been Nike's lead creative agency.
A report of Nike's split with Crispin first surfaced on Brand Republic blogger George Parker's site Adscam/The Horror.
Jeff Hicks, CEO of Crispin, confirmed the split in a statement, citing a mutual decision to part ways. He said: "We will forever be in awe of the company that is Nike and wish them nothing but the best."
Crispin's first work for Nike broke last December in the form of a 60-second Nike Plus running spot. It celebrated running in bold imagery including shots of a caveman, ancient Romans and a Native American, ending with a bunch of runners crashing through a contemporary gym wall.
Nike has also been trying out other agency partners beyond its primary relationship with Wieden, although the agency had still been handling the bulk of the business.
In January Nike handed a portion of its European football account, previously held by Wieden & Kennedy Amsterdam to the independent agency 72andSunny.