WCW Monday Nitro was created by then-WCW owner Ted Turner and Vice President Eric Bischoff, and it served as the flagship weekly show of the company.

The debut episode aired live from the Mall of America in Bloomington, Minnesota on September 4, 1995, and later editions were filmed in unusual locations such as Disney-MGM Studios in Orlando, Panama City Beach or South Padre Island for annual Spring Break-Out episodes, and even Australia and the United Kingdom in Fall 2000.

Lex Luger's surprise appearance on the debut episode was a real-life defection stunt: he wrestled his final contractual match for the WWF the night before and signed with WCW the very morning of his Nitro appearance.

The title video for the debut episode prominently featured Big Van Vader, but he never actually appeared on Nitro after parting ways with WCW following a backstage altercation with Paul Orndorff, and he left for the WWF in January 1996.

Rick Rude was the only wrestler to appear on both Nitro and Raw on the same night, since he had no WWF contract at the time; to sell the illusion that only Nitro was live, he wore a full beard on the pre-taped Raw but only a mustache on the live Nitro broadcast.

On January 4, 1999, announcer Tony Schiavone sarcastically spoiled on live TV that Mankind had just won the WWF Championship on a pre-taped Raw, causing hundreds of thousands of viewers to switch channels and hand Raw a ratings win that night.

When Alundra Blayze (Madusa) jumped to WCW in 1995, she threw the actual WWF Women's Championship belt in a trash can live on Nitro, an incident often cited as a contributing factor to the later Montreal Screwjob; WCW parodied this moment itself in 2000 when Scott Hall trashed the WCW World Television Championship.

On January 13, 1997, Nitro ended mid-match between Hollywood Hogan and The Giant, with commentator Tony Schiavone announcing the fight would continue during commercial breaks of the debuting show The New Adventures of Robin Hood, driving up that program's premiere ratings as wrestling fans tuned in.

The rock band Kiss appeared on Nitro in August 1999 and debuted a wrestler called The Demon while performing 'God of Thunder'; according to Dean Malenko, this episode drew the lowest ratings in the show's history.

In late 1999, WCW ran an eight-week nationwide competition involving 300 women to find a new Nitro Girl, with the finale held on November 8, 1999; Stacy Keibler won via internet voting and received a spot on the dance troupe plus a $10,000 cash prize.