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 territory. 
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 color seems to be green (often associated with Ireland). The gang is ruthless and has no qualms about murdering innocents, including women and children.
Events of Red Dead Redemption 2
The gang is first encountered at the Adler homestead, some members having taken shelter there 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 members. Whilst returning to their camp, the Van der Linde gang run into a lone O'Driscoll, whom 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 an gunpoint by the last remaining O'Driscoll, but is saved by Kieran shooting the man in the head. Because he saved Arthur's life, the former O'Driscoll is allowed to join the Van der Linde gang.
Meanwhile, Micah gets into a fight with some O'Driscolls at Strawberry, and is subsequently arrested for gunning two of them down. He manages to escape, however, with the help of Arthur Morgan.
Later on, the gang ambush Arthur and Micah after the two steal an armored coach. The pair manage to fight them off.
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. Unfortunately, this was a ploy to capture Arthur, so Colm could use him to lure Dutch and the rest of the gang into a trap for the Pinkertons. Luckily, Arthur manages to escape.
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 into the camp, before mounting a large attack. The gang 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 upon, 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 and 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 loses her cool 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.