Merle Dandridge portrays Marlene, a character she also portrayed in the video games. This makes her the only actor to play the same character in the show, the first game, and its sequel. Ashley Johnson, Troy Baker, and Jeffrey Pierce also star in both games (as Ellie, Joel, and Tommy respectively) and in the show, but unlike Dandridge, they will be playing different characters than the ones they originally played in the games.
When Joel (Pedro Pascal) is walking alone through the streets of Boston Quarantine Zone, a few acoustic notes of the song "Future Days" by Pearl Jam can be heard in the soundtrack. This is the song Joel plays for Ellie on his guitar in opening of The Last of Us Part 2.
The game depicts the outbreak in 2013 and then jumps forward to 2033. The show depicts the outbreak in 2003 and then jumps forward to 2023.
When Joel shifts his wardrobe to uncover his equipment under the floorboards, the camera focuses on a shot of dust particles stirred up in the air, which resemble the Cordyceps spores from the games. Spores as an infection vector were removed in the show in favour of fungal tendrils.
When the screen goes black during the plane crash scene, the game over sound effect from the game can be heard.