The show's first season production was halted in September 2007 due to the Writers Guild of America strike and did not resume airing until March 24, 2008.

Creator Sean Smith announced in March 2010 his decision to end the series after the fourth season, stating that ABC Family gave them the opportunity to wrap up the show and end it strong rather than have it cancelled abruptly.

The series was filmed primarily in Los Angeles, with location shooting at the UCLA campus in Westwood, at Caltech in Pasadena, and at the University of North Carolina at Chapel Hill.

The house used to represent the Zeta Beta Zeta sorority residence in the pilot episode is the same house used in the reality series Beauty and the Geek.

The band Plain White T's made recurring appearances throughout the series starting with the season one episode 'The Rusty Nail,' and members of the band were sometimes featured as Kappa Tau brothers on screen.

In 2009, Zach Selwyn wrote a rap song to promote the third season of Greek and shot a music video featuring the cast.

The University of Southern California initially banned the show from filming on its campus in reaction to a promotional poster featuring the Greek system's logo over a red cup, a symbol associated with alcohol consumption at parties, but held off on formally complaining to ABC Family after viewing the pilot episode and realizing the show had more depth than just partying.

Members of the real-life Greek community criticized the show's depiction of fraternity and sorority life as stereotypical.

In the United Kingdom, episodes were followed by behind-the-scenes special features called Greek Uncovered, which aired on BBC Three and were available on BBC iPlayer.