He played in Major League Baseball (MLB) for the Cleveland Indians, San Diego Padres, Oakland Athletics, Colorado Rockies and Texas Rangers.

Kouzmanoff is the third of only four players in history to hit a grand slam in his first major league at-bat, after Bill Duggleby in 1898 and Jeremy Hermida in 2005,[1] and followed by Daniel Nava in 2010.

Starting the 2006 season with Double-A Akron, Kouzmanoff flirted with a .400 average[8] before finishing at .389 and being promoted to the Buffalo Bisons in July.

[11] On November 8, 2006, Kouzmanoff was traded with pitcher Andrew Brown to San Diego in exchange for second baseman Josh Barfield.

However, he gradually increased his production and fans affectionately began to root "Koooz" when he made plays or got base hits, leading some uninitiated spectators to believe he was being booed.

[12] In 2009, he set a National League single-season record for third basemen with a .990 fielding percentage, committing three errors in 309 total chances.

[13] On January 16, 2010, Kouzmanoff and minor league infielder Eric Sogard were traded to the Oakland Athletics for outfielders Scott Hairston and Aaron Cunningham.

[16] On January 14, 2012, Kouzmanoff signed a minor league deal that included an invitation to Spring training with the Kansas City Royals.

[17] Kouzmanoff did not make it to the major leagues in 2012, instead splitting his time with Triple-A Omaha and Double-A Northwest Arkansas, where he hit .276/.309/.382 with 2 HR and 46 RBI in 90 games combined.