Gotham City has endured many a crisis. Even now, Fear State is tearing the city apart from the inside out thanks to Scarecrow and the Magistrate. Then of course there are the ordeals that various villains have put the city through, with the Joker War and City of Bane being the most recent.
However, despite the hardships these events have brought on Gotham, they're far from its worst. In fact, the worst Gotham has gone through is when it was completely destroyed - and it's happened three times!
The Destroyer
The first instance is perhaps the lesser-known of the three. This occurred in the story Batman: The Destroyer by Alan Grant, Dennis O'Neil, Norm Breyfogle, Chris Sprouse and Jim Aparo which took place across multiple Batman titles. The story begins with a number of abandoned buildings being mysteriously demolished. The perpetrator of these crimes is an individual called the Destroyer, whose motives aren't as simple as a desire for destruction - there's a purpose to his anarchy. The Dark Knight deduces that Destroyer's targets are built over buildings by the architect Cyrus Pinkney.
Fans of the Arkham video game series may be familiar with Pinkney already. The 19th Century figure designed Wonder Tower and the failed Wonder City from Arkham City and plaques dedicated to his work were collectibles in Arkham Origins. As for his comic book origins, he was commissioned by Solomon Wayne to build most of Gotham's architecture. Destroyer was obsessed with his work and shared Pinkney and Wanye's beliefs that it warded off evil. Batman was able to stop this trail of destruction, but only by demolishing yet another of the city's buildings, this one designed by the famed 19th Century architect.
Cataclysm/No Man's Land
The next and perhaps biggest event to bring Gotham City crumbling down was the Cataclysm earthquake, which led to the "No Man's Land" event. The magnitude 7.6 earthquake tore through the city making it unsafe to live in. In response, the U.S. Government evacuated the civilian population. Those who chose to stay, or were unable to leave, were sealed in when the government blew all the bridges leading into the city. After this, they declared Gotham to no longer be a part of the United States - turning it into a No Man's Land.
As a result, the criminal underworld rose up to take total control of the city. Batman himself chose to leave, believing that Bruce Wayne could campaign to restore order, but that only left the Bat-Family to protect the city alone. Though Gotham eventually pulled itself back together, it came at a great cost. Commissioner Gordon's wife Sarah Essen was killed by Joker in the chaos, something which put a strain on his relationship with the Dark Knight going forward.
Zero Year
The third and final time Gotham was totally destroyed was in the New 52 origin story for the Dark Knight, "Zero Year" by Scott Snyder and Greg Capullo. In this tale, the Ridder was the sole mastermind behind Gotham's demise, creating a lawless urban environment a lot like No Man's Land. By cutting off the city's power and using Pamela Isley's rapid plant growth formula, Edward Nygma transformed Gotham into his own personal playground. With the government unable to break his tight grip on the city, the job fell to Batman.
When a military strike force eventually did enter the city, Riddler used buildings like dominos, destroying one after another in a chain to trap his prey. When Batman eventually did stand up to him publicly, he trapped the Dark Knight in a parking lot that he had turned into a lion's den. Eventually, Gotham's heroes overpowered Nygma and restored power to the city, allowing the rebuilding to commence.
All of these events have had a major impact on Gotham, as well as Batman lore in general, and that can still be seen to this day. Whether it be references to these events in comics, or seeing them adapted in other mediums.