The Cityzens made ten changes to the side that were held 2-2 by Nottingham Forest in their Premier League clash on Wednesday, with only Matheus Nunes retaining his spot in the starting line-up.
Both teams looked lively from the onset with Tijjani Reijnders narrowly missing the target for the visitors in the opening stanza before the Magpies took the lead through Harvey Barnes in the 17th minute.
City began dominating the match in pursuit of an equalizer and levelled the score Savinho who deflected home a Jeremy Doku low ball in the 39th-minute.
Pep Guardiola's side started the second half with a bang, with Omar Marmoush finishing neatly from a Nunes pullback from the right to overturn the tie.
Toon's manager Eddie Howe made a triple substitution to try and get back into the match, but those hopes were dashed when Marmoush smashed in a long-distance strike to hand City the advantage.
City confined Newcastle to their own half for the rest of the match and were unfortunate to have not scored more goals as they advanced to the next round of the FA Cup.
"We played so good," said Pep Guardiola after the match.
"The first 20 minutes in this stadium that always happens but then Jeremy and Savinho were so decisive. The best performance we have played in this stadium in our time together here.
"It was important to score in the first few minutes of the second half but from the first 20 minutes until the end the game was really good. Everyone was so good, to beat Newcastle here is amazing."
Marco Silva has admitted Fulham endured a "very bad afternoon" after their shock FA Cup exit against Southampton on Sunday, but insisted team selection alone did not explain the defeat.
FC Barcelona midfielder Fermin Lopez has said the squad were in "good spirits" after their important La Liga victory and warned they must be ready for a demanding physical test against Newcastle United in the UEFA Champions League on Tuesday.
Mikel Arteta heaped praise on 16-year-olds Max Dowman and Marli Salmon after they helped Arsenal reach the FA Cup quarterfinals, describing their performances as “exceptional” and a sign of the pair's quality and personality.
Chelsea head coach Liam Rosenior defended his decision to heavily rotate his squad after his side needed extra time to beat Wrexham 4-2 and reach the FA Cup quarter-finals.
