The midfielder, who had been filling in at right-back due to the absences of Tino Livramento and the imminent departure of Kieran Trippier, sustained the injury to his lower right leg in training at the club's Benton facility. He will see a specialist consultant before continuing rehabilitation with Newcastle's medical team.
The club confirmed in a statement that he is expected to return for the start of pre-season.
Newcastle United said: "Lewis Miley will miss the remaining three matches of the season after fracturing his fibula. The 20-year-old midfielder sustained the injury to his lower right leg during training on Tuesday. He will travel to a specialist consultant on Wednesday before continuing his rehabilitation with the club's medical team, and is expected to return for the start of pre-season."
The timing is a bitter blow. Miley had started Newcastle's previous four Premier League matches, including a strong showing at Arsenal and a 3-1 win over Brighton on Saturday in which he kept Kaoru Mitoma largely in check at right-back.
It is the third separate injury setback of his season. He also missed seven Premier League matches between February and March with a muscle problem following an initial dead leg, and had previously suffered a broken metatarsal during his development years.
Miley has made 34 appearances in all competitions this term, scoring once and contributing four assists across 15 Premier League starts. He also featured seven times in the Champions League.
Newcastle currently sit 13th in the table and face Nottingham Forest, West Ham United and Everton in their remaining fixtures.