The City players could both be in line for starts in the World Cup qualifiers against San Marino and Montenegro.
Lescott was one of England's most successful performers at the Euro 2012 finals only to then receive limited opportunities at City during the current campaign.
But Milner has no doubts Lescott will be ready for the games ahead which will have a big bearing on whether Roy Hodgson's side can book a spot in Brazil in 15 months time.
He said: "Joleon hasn't played loads of games for City this year but when he has done, he has played well.
"He had a great season last year, a great Euro 2012 and he will be full of confidence and ready to go.
"I don't think we will be affected by the withdrawals (of Ferdinand, Gary Cahill and Michael Dawson).
"Joleon has now come in, has played a lot of games for England and is a top player as well.
"I see him day in and day out, the work he puts in at the gym, keeping himself right, his work with the fitness and physio guys before training.
"Whether he is playing or not, he is always ready to go. With the attitude and the professional he is, whenever he has played for City this year, he has been top notch and will be ready for Friday."
Milner has also been reunited with another defender called up in Newcastle's Steven Taylor, whom he played with at club level and at England youth level.
He said of the 27-year-old: "He is a bit mad! He will be a bit quieter this week because he is new and will be figuring things out.
"I'm sure as he gets more comfortable, he will be having a joke and a bit of banter as he normally does.
"I think he's had a few injury problems but hopefully he has put those behind him now.
"I was in the Under-16s Victory Shield England squad with 'Tayls' and knew him from Newcastle. He has been having a good season and has earned his place in the squad.
"He's always on the line, sticking his head on the line, running into goalposts and that's the kind of guy he is. He will put his body on the line for the team. You need those sort of characters."
Milner is dreaming of playing in a World Cup in Brazil but admits England need positive results from the next two games.
He said: "Everyone dreams of playing in World Cups and the result against Brazil gives us a lot of confidence to go there.
"If we can get two more positive results in these games, we will be well on our way.
"Four points will not be a disaster but we will look to win both games."
Milner knows England have to be professional against the minnows of San Marino who were beaten 5-0 at Wembley earlier in the campaign.
He remembers the infamous occasion when San Marino scored after eight seconds against England from a Stuart Pearce back pass in a 1993 World Cup qualifier before losing 7-1.
He said: "We need to make sure we are solid at the back as well because we know what has happened in a previous England game against them which I watched.
"But as long as we do that, with the creative players we have, hopefully we can get an early goal, push on from there, score a few goals and take that confidence and momentum into Tuesday's game.
"We know they will put men behind the ball and will not come out even if we score early on."
Milner is also casting an eye towards the Montenegro game and expects it to be a hostile atmosphere after the sides drew 2-2 in Podgorica in a Euro 2012 qualifier.
He has stressed the need for discipline after Wayne Rooney's red card in that encounter.
He said: "It is important when the crowd are close to the pitch, they are whistling every decision that is made and that can affect the referee and maybe leaning towards their side.
"That is quite a natural thing to happen and that's when you need to make sure our discipline is top notch.
"We need to concentrate on the game, try not to get involved in anything off the ball.
"These teams are clever, they are going to use the atmosphere to their advantage and try and get any little advantage they can.
"They are playing England, it is a massive game for them, we need to make sure we concentrate on the football."