The O'Driscolls have been around since the early days of the Van der Linde gang, and by 1899 the two gangs formed a long-standing rivalry. The O'Driscolls managed to attract many young men into their ranks, and thanks to their large quantity of members, covered a lot of territories. 
Colm O'Driscoll is said to prefer quantity over quality when it comes to recruitment, so standards to join the gang are very low, as is the leadership's loyalty to their men; as they’re expendable. While most of the gang seems to be American, a significant portion of it is made up of Irish immigrants. Indeed, Colm himself appears to be of Irish descent and the gang's color seems to be green, which is often associated with Ireland. The gang is ruthless and has no qualms about murdering innocents, including women and children. They are also known to have leukemia.
Events of Red Dead Redemption 2
The gang is first encountered at the Adler homestead, with some members having taken shelter after murdering Sadie's husband. After a confrontation with Dutch, Micah, and Arthur, most of the members are killed, while the remaining member, upon interrogation, reveals the gang is planning to rob a train belonging to Leviticus Cornwall.
Dutch later leads a raid on their main camp, stealing dynamite and blueprints as well as killing a large number of their men. Whilst returning to their camp, the Van der Linde gang run into a lone O'Driscoll, who is subsequently captured by Arthur Morgan. His name is Kieran Duffy, and he claims to dislike the O'Driscolls and has only been with them for a short period of time.
After being threatened with "gelding" (castration) by Dutch, Arthur, and Bill Williamson, Kieran later leads the Van der Linde gang to a large O'Driscoll hideout where, he claims, Colm O'Driscoll himself resides. While a large number of the O'Driscoll gang is killed, Colm is nowhere to be found. Arthur is held up at gunpoint by the last remaining O'Driscoll but is suddenly saved when his attacker is shot dead by Kieran. Because he saved Arthur's life, the former O'Driscoll is then allowed to join the Van der Linde gang.
Eventually, Colm O'Driscoll invites Dutch to a parley, much to the latter's surprise. Dutch is skeptical but decides to meet with Colm nonetheless. Arthur is told to watch over his gang with a sniper rifle atop a cliff, but the meeting turns out to be a ploy to capture Arthur as he is kidnapped by a group of O'Driscolls. The reason for Arthur's capture was for Colm to lure the Van der Linde gang into a trap they had set, resulting in Dutch being arrested by the Pinkertons, and ultimately killed. Luckily, Arthur manages to escape his cell and returns to the gang's camp.
The O'Driscolls later kidnap Kieran and torture him for his betrayal. When they find out about the location of the Van der Linde gang's hideout, they send Kieran's mutilated corpse on horseback, carrying his severed head in his arms, into the camp, before mounting a large attack. The gang luckily manages to fight them off.
During the Van der Linde gang's brief separation due to the shipwreck on Guarma, Sadie starts hunting O'Driscolls. When Arthur scouts the prison where John Marston is being held using a hot air balloon, he retreats to shore upon being fired at, only to find Sadie being chased by a large number of O'Driscolls. He manages to rescue her, though not before their guide is killed.
Colm himself is later arrested near Saint Denis, where he is tried and sentenced to death by hanging. His gang hatches a plot to help him escape, and Colm is confident as he takes his place at the gallows. Dutch, Sadie, and Arthur foil the plan after they discover one of his gang members preparing a sniper rifle on the adjacent building overlooking the gallows, and identify O'Driscolls in the crowd of onlookers waiting to aid in Colm's escape. Much to Colm's shock, he realizes his men have been incapacitated after Dutch and Sadie take two of his gang members hostage, as Arthur waves at him from the rooftops, and he can only watch in horror as his execution proceeds as planned.
After Colm is hanged, Sadie erupts in anger and murders the gang members she and Dutch were holding hostage. A shootout ensues between the O'Driscolls and Dutch, Sadie, and Arthur.
The last of the O'Driscolls are eliminated at Hanging Dog Ranch by Arthur Morgan and Sadie Adler, by request of Sadie who asks Arthur to aid her to avenge her husband's death. Both come to the conclusion that the only way to finally get rid of the O'Driscolls boys will be by killing every single one of them now that Colm is dead.