The 1981 wedding of Luke and Laura drew about 30 million viewers, making it the most-watched hour in American daytime soap opera history.

The show's original concept, as described by star John Beradino, was like a big wagon wheel where the spokes were the characters and the hub was the hospital.

The city setting of Port Charles was not actually named on-air until the late 1970s, even though the series began in 1963; early episodes simply referred to an unnamed midsize Eastern city.

When ABC expanded General Hospital to a full hour in 1978 to save it from cancellation, producers were given only six months to improve the ratings.

New executive producer Gloria Monty spent an extra $100,000 re-taping four episodes on her very first day on the job in 1978, which helped turn the show's fortunes around.

During the 1980s, the show did location shooting at real landmarks including Mount Rushmore, Niagara Falls, the Grand Ole Opry in Nashville, Atlantic City, Catalina Island, and San Antonio.

General Hospital has been parodied or referenced in numerous other media, including Mystery Science Theater 3000, the film Tootsie, The Muppet Show's 'Veterinarian's Hospital' sketch, Mad TV, and the Fox series House, where Dr. House watches a parody show called Prescription Passion.

Production was suspended in March 2020 due to the COVID-19 pandemic and resumed on July 22, 2020, making General Hospital the first Disney series to return to production during the pandemic.