The Gunners were forced to change to a new bus as Blackpool supporters continue to protest the club's owner Owen Oyston.
One Blackpool fan climbed on top of the coach, while several others stood in its way in an effort to prevent the bus from leaving the hotel and heading to Bloomfield Road.
Blackpool supporters saw the high-profile FA Cup showdown as an opportunity to have their protests against Oyston given a bigger platform, with the game broadcast on national television.
Protests are expected outside of Bloomfield Road ahead of the game as Tangerines supporters voice their opposition to Oyston's ownership.
Inside the ground, however, it should be a more subdued environment with Blackpool having sold less than 3,000 tickets to the FA Cup match.
The small number of home supporters is nothing new for the League One side, whose average attendance is less than 4,000 this season as fans continue to stay away due to their opposition to Oyston's ownership.
Police were aware of the potential for protests before the game, with particular attention paid to pitch invaders.
“Anybody entering the field of play without permission will be committing criminal offences and will be dealt with appropriately," a Lancashire Police statement published ahead of the match read.
Blackpool fan group, The Muckers, said: "We are calling on all Blackpool fans to make their feelings known towards the owners in a non-violent but direct way.
"We will be present and encourage people not to enter the pitch, which we would condemn."
Arsenal have sold out their allocation of 5,300 tickets, meaning the away side will likely have more supporters at Saturday's match, which kicks off at 5:30pm local time.