In "Life of Brian", After Stewie and Brian travel back to the 17th century in Stewie's time machine and give the Indians guns, they travel back to fix their mistake. Later after Stewie realizes the dangers of time travel, he decides to take his time machine apart and never time travel again. After taking it apart, Stewie ask Brian to help him haul it off to the dump so he can crush it down and won't be able to put it back together. While at the dump, Stewie and Brian find a street hockey net and take home so they can play with it. While Brian sets up the net, an unknown assassin rounds about the corner in a car and runs Brian over, fatally injuring him, and ruining the net, Brian's death hits the whole family hard and they bury him.
In "Mobsters Inc.", Brian's death is shown again in the stock footage, recapping the events of the previous episode.
In "It's in the Yard", Stewie looks around Quahog, interrogating everyone to find the person who killed Brian, all to no avail. Stewie uncovers traffic light camera footage of the incident and captures the event at a new angle, but again, finds nothing.
In "Christmas Guy", While Stewie was sitting on Santa's lap at the Quahog Christmas Carnival, Santa asks Stewie what he wants for Christmas. After thinking for a while, Stewie realizes that he wants Brian back. Stewie is sad without Brian and doesn't know how to bring him back. However while at the mall, he discovers a past version of himself with the old return pad of his time machine.
He soon recalls a cutaway gag in "Life of Brian" before Brian's death, where Stewie told him [Brian] that he [Stewie] traveled ahead to Christmas to purchase a toy so he would not have to wait for it. The events of that cutaway actually happened. Stewie then steals the other Stewie's return pad, knowing that he can use it to travel back to before Brian was killed and save him.
Once Stewie time travels back to before Brian died, he sees Brian on the road with the street hockey net and then sees the car driver that originally ran him over round about the corner like before. And this time, Stewie pushes Brian out of the way of the car and saves him. However the net is still ruined. Stewie then tells Brian about how the car killed him, and that how he traveled back to save him and Brian thanks him for saving his life.
Afterward, Brian realizes Stewie is starting to fade away. Stewie tells Brain that now that he's saved him, the timeline that the car driver created with Brian's death no longer exists. Future Stewie then wishes Brian a Merry Christmas and disappears. Afterward "Life of Brian" Stewie walks out and asks Brian "Hey who are you talking to out here?" to which Brian replies "A pretty awesome guy."
In "No Giggity, No Doubt", it, along with a slew of other characters appear as one of the potential candidates for going on the camping trip with Quagmire and Courtney. Peter mentions this unknown assailant too, as "The car that killed Brian". Canonically, there is no way he could have this knowledge, given how this happened in an alternate timeline that was erased from history but this was nothing but a gag, so it doesn't really matter.
In "Cat Fight", Brian walks backwards into the street, in an attempt to mysteriously disappear behind a passing by bus, only to fail to walk back far enough and get hit. After getting hit, Brian lands on the sidewalk, painfully damaged and covered in blood. Afterward, the car driver happens to drive past him on the street, eerily alluding to how previously, he was fatally hit by this same car in the same area to a much worse effect.
Who is the Car Driver?
So far, it is unclear who the driver is and it will likely never be revealed. Several fan theories have been made as to who the driver was and why he/she would have killed Brian.
Some theories suggest that Glenn Quagmire was the murderer. Quagmire utterly hates Brian and doesn't care about him at all, as was first revealed in "Jerome is the New Black". In fact, he sees him as less than human and wouldn't care if he died. He once beat him nearly to death, proving that he'd be perfectly fine with killing him.
In "Dog Gone", Brian ran over and killed a dog, while drunk driving in a fashion not too different than the way the driver did, when killing him. When Brian confessed what he did to the police, he was laughed at and told that killing a dog isn't illegal because they're not human beings. Offended by this concept, Brian protested against this, which only turned this into public knowledge among everyone he knew, including Quagmire. That being said, Quagmire would know that he could kill Brian without suffering any consequences, prompting to do what he did.
However, there doesn't seem to be any as-of-then recent events that would have pissed Quagmire off to kill him at that particular moment. His hatred would have remained static until Brian might have done something before then. Quagmire also didn't seem to exhibit any care for Brian's death, as he was on his phone at his funeral, completely zoned out. It's possible that Quagmire attended Brian's funeral to hide the fact that he was the killer, but didn't want to look suspicious, so he stayed in character as a guy who hated Brian, so nobody would notice his strange behavior. If that's the case, then Quagmire must have killed Brian, and he's just really good at hiding it or maybe the only reason Quagmire went to the funeral was because his father did, having been an ex-lover of Brian's, making him feel obligated to do so as well.
Another fact that may debunk this theory would be that if it was really Quagmire who killed him, then in the timeline, where Stewie saved Brian, Quagmire's murder attempt would have failed, which would have led him to make another murder attempt in the future. Since then, no future murder attempts have happened to Brian, let alone from Quagmire, so it's not likely this is the case.
All in all, Quagmire has hated Brian Griffin long before and long after the event of his death (or near-death experience), and nowhere along the way has he ever expressed the urge to kill him. It would seem odd that Quagmire would randomly make one attempt at killing Brian only to abruptly forget about it from then on.
Some fans assume that the driver was Vinny, the dog whom the Griffins adopted a month after Brian's demise in "Life of Brian". This is a strange theory, as it would suggest that Vinny somehow knew about The Griffin Family beforehand and for whatever reason, wanted to join the family. So, he decided to take it upon himself to kill Brian so that he could take his place. As far as the show's lore is concerned, Vinny has mainly been caged in the pet store and would have no way of knowing about The Griffin Family and even if he did know about them, why would he specifically want to be with them? This would also mean he'd have to be a pretty good actor, to pretend he'd never met them before, in the scene where they adopt him.
The idea of Vinny killing someone else isn't too far-fetched however, since he does have a history of being an Italian mobster, who has done such things to people in the past. It is possible that somebody hired Vinny as a hitman, (Quagmire, some would theorize) and sent him to kill Brian. Somewhere in he timespan of the few months between the death of Brian and the adoption of Vinny, the latter might have been incarcerated in the pet store and coincidentally adopted by the family of the same dog he killed. Vinny didn't comment on this either because he was hiding it or because he'd killed so many other people since then, he didn't even remember.
Theories suggest that Ernie the Giant Chicken killed Brian, as he thought of it as a way to hurt Peter, where it hurt the most. This theory is somewhat flawed as the more reasonable crime would be for Ernie to hit Peter with the car. Ernie has never expressed any hatred toward any other members of Peter's family and all of his attacks on his rival have been rather direct and very rarely if ever something to be described as a "master plan", which is how the crime mentioned in this theory can be accurately described.
In "Follow the Money", Ernie was shown to be friends with Lois. If Ernie really had the intention of hurting one of Peter's loved ones, it would seem unlikely for him to maintain a friendship with his wife. That being said, this makes it even more unlikely that he killed Brian for the reasons mentioned before.
Overall, the theory of Ernie being the murderer of Brian is bogus from a logical standpoint, as Ernie's actions in this theory are both out of character and fueled by misplaced retribution.
Others suggest that the person driving the car was not any previously established character but rather, a person who's never been seen before. It's most commonly suggested that this person was a drunk driver, who had no intention of killing anyone but ended up doing so, as he/she was intoxicated and recklessly driving. This would explain the swerving of the car as it somewhat uncontrollably veered down the road.
The only people we know couldn't have killed him are all members of the immediate Griffin family, since they were either witnessing the event when it happened, or were the person getting killed by said car.
- Life of Brian
- Mobsters Inc. (Stock Footage)
- It's in the Yard (Pictured; Video)
- Christmas Guy
- No Giggity, No Doubt (Non-Speaking Cameo)
- Cat Fight (Non-Speaking Cameo)
- The car that struck brian was a 2010 Mercedes-Benz E-Class coupe.