Fernandes, 30, assisted both of Man United's opening goals at home to Everton, first for Marcus Rashford and secondly for Joshua Zirkzee.
The Portuguese midfielder has now provided more assists than any other player from his country in Premier League history.
His two against Everton overtook Manchester City's Bernardo Silva with 45, to hand Fernandes his 45th and 46th assists in the top-flight.
Nani sits in third with 43, all of which came across his eight-year tenure at Manchester United.
Cristiano Ronaldo was in fourth. He earnt 37 assists during his two spells with Manchester United.
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Fernandes has now scored twice and assisted five times in the top-flight this season.
The record could be set to change however, with Manchester City in action later on Saturday against Liverpool at Anfield, where Bernardo Silva could match or exceed Fernandes' tally.
Portugal internationals have typically fared well in the English top-flight, with the likes of Nani and Ronaldo collectively making over 380 appearances in the league.
Nani scored 26 goals for Man United, whilst Ronaldo netted over 100 times.
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Fernandes joined Man United in 2020 from Sporting for a fee of £67million after he had an electric season in the Portuguese top-flight as the top scoring midfielder in Europe.
During his time in Manchester, Fernandes has won the FA Cup once last season and the League Cup in 2022-23.
Man United have begun to find their feet under new boss Ruben Amorim, with their first victory coming in the Europa League against Bodo/Glimt.
Amorim's side have a tough test ahead as they travel to Arsenal on Wednesday in the top-flight.
Thereafter they face Nottingham Forest at home.