Lou is Sal Marcano's older brother. He got his start slinging dope before serving time in Cordoba along with the rest of his brothers.
Following his release from prison, Lou set up shop as a pimp in the French Ward district of New Bordeaux and aided his brother, Sal, with a bloody takeover of the Carillo Family.
Lou's reputation, along with the rest of his brothers, especially Sal, advanced to the point where their family was put on the map with the Commission.
Lou is in charge of grooming politicians and bigwigs of New Bordeaux to use for their advantage; according to Jonathan Maguire he established ties to various influential figures within New Bordeaux including politicians, lawyers, bankers and merchants, using his accountant Tony Derazio to bribe corrupt city government officials.
Lou, who insisted on being called "Uncle Lou", built all of his rackets in the French Ward district for the VIP and special clientele privileges, offering more 'exotic' choices to anyone that would pay the right amount of cash. Building an image within the French Ward and around New Bordeaux, Lou expanded into legitimate businesses such as bars and restaurants around the district and becoming the face of the city as 'Uncle Lou'.
In 1968, Lincoln Clay sabotaged and took over Lou's prostitution and narcotics rackets within the French Ward district, intent on eventually getting his chance to murder Lou.
After Lincoln murdered his accountant, Tony Derazio, and stole his ledger, he and Donovan realised that Lou was bribing district judge Cornelius Holden, in order to overturn the state ban on gambling at the behest of Lou's brother Sal, who wanted to open a casino in the city.
Donovan later intercepted a wiretap between Holden and "Uncle Lou", which revealed that Holden was fearing for his safety after learning of Lincoln's attacks against the Marcano family empire, spurring Lou to send some of his best men in an armoured car to protect and escort Holden from the trial of Hollis Dupree. Ultimately they fail and Lincoln kills Holden, which infuriates Sal, who threatens to have Lou clipped unless he can rectify the situation.
Lou informs Sal of another candidate, Senator Walter Jacobs, who is also part of the clientele at his prostitution ring. Lou agrees to arrange a fundraiser for the Senator on-board his riverboat, the Delphine, which is interrupted by Lincoln, who kills Lou's security before confronting Lou; although he tries to take the Senator hostage at gunpoint, an explosion throws both Lincoln and Lou out of the riverboat, killing the rest of the passengers including Senator Jacobs, who catches fire.
Lincoln, having lost his firearms but armed with his combat knife, pursues Lou through the swamp, eventually catching up to him and slitting his throat. He later hangs him for public display from the Andrew Jackson Statue, with a Re-Elect Jacobs sign on his chest, as a message to Marcano.
- Sal Marcano (brother, deceased)
- Tommy Marcano (brother, deceased)
- Giorgi Marcano (nephew, deceased)
- Olivia Marcano (sister-in-law, deceased)
- Lucio Marcano (brother, deceased)
- Michael Grecco (nephew, deceased)
- Valerio Marcano (father, deceased)
- Virginia Marcano (sister-in-law)
- He is referred to as the "unofficial mayor" or "Santa Claus" of the French Ward.
- He is happy to help Giorgi and Ellis sell heroin on the streets of the French Ward.
- Lou is the eldest of the Marcano brothers.