He played in Major League Baseball (MLB) for the Philadelphia Phillies, Arizona Diamondbacks, Pittsburgh Pirates, and New York Yankees.

Zagurski also played in Nippon Professional Baseball (NPB) for the Hiroshima Toyo Carp and Yokohama DeNA BayStars.

[1] Almost 60 of the pitcher's friends, former teammates, and family were in attendance at Zagurski's first major league appearance at the Atlanta Braves' Turner Field.

On the possibility of pitching to the potential future Hall of Famer, Zagurski had said, "Having an opportunity to face [Bonds] would be awesome.

I'm sure I would notice him, but he's still trying to hit the ball and I'm still trying to get him out, so I think the star-strucking will stop"[3] On June 7, Zagurski won his first major league game as the Phillies completed a three-game sweep of the first-place New York Mets at Shea Stadium.

Phillies color commentator Gary Matthews said Zagurski believed he had a place in the major leagues and that the young pitcher was "not at all in awe of being here."

The game, which was carried nationally on ESPN's Sunday Night Baseball, saw the St. Louis Cardinals beat the Phillies 10–2.

On July 27, Myers was activated from the 15-day disabled list and the Phillies optioned Zagurski to the Triple-A Ottawa Lynx.

Zagurski started the 2010 season with the Lehigh Valley IronPigs, the Triple-A Affiliate of the Phillies, and was recalled to the major league club on June 22, 2010.

On October 3, Zagurski was removed from the 40-man roster and sent outright to the Triple-A Scranton/Wilkes-Barre RailRiders; he subsequently rejected the assignment and elected free agency the next day.

Three days later, Zagurski made his first Major League appearance since the 2013 season, earning his first career loss against the Cincinnati Reds.

This set the MLB record for the longest time between a pitcher's first career win and loss at 11 years, 23 days.