Although PNE had tasted success in the FA Cup, it was their only win against Boro in 17 games from 1972 all the way through to 2019.
In the end, a 2-1 win at the Riverside gave the Lilwyhites, then playing in green, the win for boss Alex Neil.
Ashley Fletcher opened the scoring for the home side before a Paul Gallagher free kick levelled things up. Daniel Ayala was sent off just after the hour with Jayden Stockley scoring a header with just nine minutes to go to seal all three points.
5. Gally celebrates
Preston North End's Paul Gallagher celebrates scoring his side's first goal with teammates. Photo: CameraSport - Alex Dodd
6. Stockley gets the winner
Preston North End's Jayden Stockley scores the winning goal. Photo: CameraSport - Alex Dodd
7. Alex Neil after the win
Preston North End manager Alex Neil celebrates after the match. Photo: CameraSport - Alex Dodd
8. Stockley and Seani celebrate
Preston North End's Jayden Stockley celebrates scoring the winning goal with Sean Maguire. Photo: CameraSport - Alex Dodd