The idea for a comedy about an immigrant in America was initially rejected by all three major US networks (ABC, CBS, NBC), and was inspired in part by the wave of patriotic sentiment following the 1984 Summer Olympics in Los Angeles.

The show was originally titled 'The Greenhorn' and was greenlit around Bronson Pinchot after his attention-grabbing role as Serge in Beverly Hills Cop, but Pinchot was unavailable at the time due to a role in the NBC series Sara.

Comedian Louie Anderson was originally cast as Larry and a pilot was even produced with him, but he was ultimately deemed not right for the role before Mark Linn-Baker was cast after producers saw him in a guest appearance on Moonlighting.

ABC President Brandon Stoddard gave the show a prime tryout slot in spring 1986 airing between two hit shows, Who's the Boss? and Moonlighting, which helped it become an instant ratings hit.

The new location footage used in the season 3-8 opening credits, including shots around Chicago landmarks like Wrigley Field and the Chicago Theatre, was filmed on September 11 and 12, 1987.

The apartment building used for exterior shots in the first two seasons was the now-demolished Santa Rita Hotel in downtown Los Angeles, while the Chicago Chronicle building was actually the London Guarantee Building at 360 North Michigan Avenue in Chicago.

The theme song 'Nothing's Gonna Stop Me Now' was written by Jesse Frederick and Bennett Salvay, who also composed themes for other Miller-Boyett shows like Full House and Family Matters, and was performed by David Pomeranz.

A planned recurring child character, Tess Holland (Alisan Porter), was introduced in season 6 and even credited in the opening titles, but was abruptly dropped and never seen again after her first appearance, partly due to network pressure to add younger characters to the TGIF lineup.

In German dubbing, Balki's backstory was changed so that he was an actual Greek from a Greek island rather than from the fictional island of Mypos, and the show was retitled 'Ein Grieche erobert Chicago' (A Greek Conquers Chicago), with Balki speaking without any foreign accent.

In Brazil, the character Balki was renamed 'Zeca' and made Brazilian from Minas Gerais, with the show retitled 'Primo Cruzado' after the Brazilian currency of the time.

The HBO series The Leftovers featured Mark Linn-Baker as himself, depicting a world where the entire cast of Perfect Strangers had vanished in a mass disappearance event except for him, who had faked his own disappearance.

Home video releases of the series were delayed for years due to high music licensing costs, since certain episodes featured popular songs; however, these were usually not the original recordings but a cappella versions sung by Mark Linn-Baker and/or Bronson Pinchot in character.