Manning was born in Chicago, Illinois. After finishing school he pursued a career in fashion, posing for numerous advertising campaigns, including those for well-known fashion companies, and independent films. He stated on his April 17, 2007 appearance on The Howard Stern Show that he also formerly worked on Wall Street and has a Masters Degree.[2] In a 2004 New York Times article, it was stated that Nick Manning was a former human resources executive at Citigroup in New York, who was recruited off the street as a model.

Manning began his career in the adult film industry in 2000 appearing in the movie Daytime Drama. Since this role, he has appeared in over 500 adult films and developed a catchphrase, "ahhhhhhhh dropping (fucking) loads" which he says as he ejaculates. Manning is known for his often quirky comments while performing. Some cult favorites include "Take your fucking!", "That's how I like it, you're just layin' there gettin' fucked, not sayin' much", "Cubs win!", "Palumbo you chode!", (when ejaculating into a mouth) "Your teeth are melting you filthy whore!", "Welcome to the Filth Factory," "Where's Harvey Dent?!", "Eat shit!", "Edward James Olmos", "On your knees and polish my helmet skank!", "Make my cock a steeple", "Lick Lenny's face, whore", "Dropping loads and taking names", "Beat that cock and make it sing", and "Another load dropped... with vengeance!". In 2003, he was awarded Best Male Newcomer by Adult Video News. He is currently represented by LA Direct Models.

He also owns a production company, BoneYard pictures, and owns shares in Platinum Blue Productions, which produces the popular Fans Have Spoken series, in which Nick and other stars perform sex scenes per the specifications and suggestions of members of his online website. He also co-owns Platinum Blue Productions with fellow adult film actress/director Skye Blue (Lorri Moore). He has directed several adult films including The Fans Have Spoken 4 and Beauty Within.

Manning has a line of male sex toys bearing his name, Nick Manning's Masturstroke Kit (a masturbation device/penis enlarger or penis pump) and Nick Manning's Body Slam Masturbator. Sound clips of his voice have been used for comedy bits on The Howard Stern Show. He appeared as the DJ in porn star Brittaney Starr's music video "I Wanna Fuck the DJ."

"I went to New York, Milan, Paris, London, Johannesburg, and Capetown as my modeling career took off and I became a Supermodel.Having done ad campaigns for Nautica®, Versace®, Armani®, and Hugo Boss® among others, as well as almost every major fitness magazine, and over 100 national network commercials.I then went on to star in several independent film, television shows and feature films.This led me back to New York, Miami and eventually L.A.…Now, you may ask: "what the hell is a guy with these kind of experiences and education doing shooting porn?" But the answer is painfully simple… I REALLY like sex!"