The story begins with Johnny Klebitz and all the members of the famous biker gang, The Lost MC, driving through the streets of Alderney at night. In a brief cameo, Niko Bellic, the main character of GTA IV, swears at a passer-by on the street as the gang drives past.
Johnny is the vice president of the gang, but has been the acting president for a year due to the club’s president, Billy Grey, who has been in court-ordered rehab after being arrested for narcotics possession. As leader, Johnny has established The Lost throughout Liberty City by making truces and deals after suffering several financial troubles, mainly caused by Billy’s poor leadership. The most notable truce is with The Lost’s rivals, The Angels of Death, which has allowed The Lost to operate their drug deals and gun running operations more freely.
On being released from rehab, Billy immediately reverts to a life of crime and tensions quickly grow between Billy and Johnny, who believe the gang should go different ways. Johnny wants to keep the gang running smoothly, deeming war with other gangs as immature and bad for business, whereas Billy prefers acts of random violence and mayhem. As such, Billy quickly leads the Lost to assault the Angels of Death Clubhouse, beginning a gang war against the Angels of Death, which serves as the main backdrop for the game.
Meanwhile Johnny does business with drug dealer Elizabeta Torres and import bikers Malc and DeSean. He is also entrapped by Congressman Thomas Stubbs III into committing several assassinations and planting a bug in the car of Deputy Mayor Bryce Dawkins (which is given to Niko Bellic by Bernie Crane soon after in Grand Theft Auto IV). From time to time Johnny is led to help his ex-girlfriend Ashley, a drug addict who constantly gets herself into trouble, including saving her from a group of thugs and paying off her debts to Dimitri Rascalov by kidnapping Roman Bellic.
Eventually, Billy is arrested after a failed drug deal with the Triads (which was actually partly set up by Billy, as revealed in the Ballad of Gay Tony) and Johnny takes over as President of The Lost. This immediately sparks a civil war within the gang, one side with Johnny, the other with secretary Brian Jeremy, who is still faithful to Billy and believes Johnny to be responsible for Billy’s arrest. Brian stages a coup against Johnny in which most of the Lost are killed. Johnny and his friends manage to come out on top, but Brian escapes. Soon after mafia capo Ray Boccino sells Brian’s location to Johnny in the interest of stabilizing his business with the Lost. Johnny goes to the safehouse and kills Brian along with the last of his goons, putting an end to the civil war.
After killing Brian, Johnny repays Boccino by stealing $2 million worth of diamonds for him from Anthony “Gay Tony” Prince (while killing Tony’s boyfriend Evan Moss in the process). When Johnny tries to collect his share of the diamond money, he becomes part of the infamous diamond deal seen in Grand Theft Auto IV, and manages to get away with all of the $2 million that Boccino was to receive for the diamonds. Johnny gives the money to the Lost’s treasurer Jim Fitzgerald. Soon after both Jim and Johnny are held captive by Boccino, but fight their way free and are pursued by Boccino’s men. Johnny leads his pursuers into an ambush in Alderney. However, when he returns to the Lost Clubhouse, Johnny learns from Ashley that Jim has been killed (by Niko Bellic).
Shortly after, Stubbs reveals that Billy is planning to testify against the Lost, pin all its crimes on Johnny, and enter Witness Protection Program. Johnny leads the remaining members of the Lost in a daring raid on the state prison in Alderney, where Billy is being detained, and personally executes him. With Billy dead, the surviving members of the Lost return to their clubhouse, where it is revealed that the only surviving members are Johnny, Clay Simons, Terry Thorpe and the paraplegic Angus Martin. With their club and brotherhood destroyed, they decide to burn the clubhouse to the ground. The last shot is of them watching it burn, contemplating what comes next. Ashley promises Johnny that she will enter rehab, with Johnny wishing her the best.
At several points throughout the course of the game, the plot intertwines with events from Grand Theft Auto IV and is seen and played out from Johnny’s perspective. These include Elizabeta’s drug deal gone awry, and Ray Boccino’s diamond operation (both of which were played from Niko’s perspective in the main game). It is revealed that it was Johnny who kidnapped Roman Bellic and took him to the warehouse in Bohan where Niko eventually rescued him in the main game (Roman briefly hints this in a text message). It is also revealed that a seemingly random biker that Niko killed for Ray Boccino in the main game was actually Johnny’s best friend, Jim Fitzgerald (in the mission No Way on the Subway). Also, Niko’s killing of The Lost member Jason Michaels under orders from Mikhail Faustin is blamed on The Angels of Death by Billy Grey, who uses it as an excuse to re-ignite the gang war between them. The ending movie shows key points in the original story line, such as Niko and Roman finding their home and cab business destroyed, and Niko executing Vlad, with The Lost riding in the background. One of the missions also involves Tony Prince from The Ballad of Gay Tony, including the trading of Ray Bulgarin’s diamonds, and provides Johnny’s perspective to the first piece of plot to that expansion’s storyline.