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The National League hosts were impressive in the first half, and almost took the lead through John McCombe's overhead kick, which went narrowly wide.
They continued to press and midfielder Paul Lewis could not find the target when in a good position inside the box, before Jack Mackreth shot over from close range.
Oxford threatened themselves, and Marvin Johnson's cross struck the top of the crossbar in the second half before Chey Dunkley's header rattled the post.
Visiting goalkeeper Simon Eastwood brilliantly kept out Chris Holroyd's low effort, before Mackreth hit the post late on.
Oxford, who reached the fourth round last year, will need to improve significantly for the replay at the Kassam Stadium on Tuesday, 13 December.
Former England midfielder Trevor Sinclair on BBC Two:
"Oxford boss Michael Appleton will be disappointed - they were playing against a team two leagues below and have not really turned up. They have been fortunate to get through this match and I am sure they will play better in the replay.
"Maybe Appleton will learn something from this as they have come a long way on the morning of the match and the players looked a bit leggy."
Macclesfield manager John Askey on BBC Two: "On another occasion, things could have gone for us and we could have got the win.
"Overall we played well, created a lot of chances, but needed a better final ball or finish. We had a little wobble for five minutes but I can't ask any more of the players.
"I don't think the gap between the EFL and non-league is as big as it used to be. There are a lot of full-time teams. We showed that we have got decent players.
"It will be difficult there in the replay. On home soil, Oxford will be a different proposition. We will have nothing to lose and if we can get a win it would be great."
Macclesfield winger Jack Mackreth: "We put in everything and deserved to win the game.
"We are happy with a draw. Hopefully we can go to their place and get a result. Our movement was good and we created a lot of chances."
Oxford head coach Michael Appleton: "A few of our younger players were shell-shocked at half-time. They showed spirit and quality in the first half and got after us. They made it very difficult.
"When you come to a National League side, it is tight. They had a lot of quality.
"We were very, very, very, poor. I am not stupid enough to think any different. I would like to see us play better in the replay.
"I have got to pick a better team in terms of the right personnel.
"Let's hope we get a tie that generates a bit of excitement and make sure both teams have everything to play for in the replay."
Ian Meatcher: Great performance from the non-league side. Not quite the cup upset we all wanted. Macclesfield Town are in the hat though.
Jamie: Macclesfield were excellent - real shame not to get the win but great result all the same. Onwards and hopefully upwards.
Elliot Owens: Can't believe that game finished 0-0. Perhaps a league side would have put away those chances and knocked Oxford out.
Match ends, Macclesfield Town 0, Oxford United 0.
Second Half ends, Macclesfield Town 0, Oxford United 0.
Attempt missed. Chris Maguire (Oxford United) right footed shot from outside the box is too high from a direct free kick.
Alexander MacDonald (Oxford United) wins a free kick in the attacking half.
Foul by John McCombe (Macclesfield Town).
Offside, Macclesfield Town. Craig Ross tries a through ball, but John McCombe is caught offside.
Offside, Oxford United. Marvin Johnson tries a through ball, but Kane Hemmings is caught offside.
Chris Maguire (Oxford United) wins a free kick in the defensive half.
Foul by Paul Lewis (Macclesfield Town).
Jack Mackreth (Macclesfield Town) hits the left post with a right footed shot from the right side of the box. Assisted by Danny M. Rowe with a cross.
Attempt missed. Ryan Taylor (Oxford United) header from the centre of the box misses to the left. Assisted by Marvin Johnson with a cross.
Substitution, Oxford United. Kane Hemmings replaces Tyler Roberts.
Mitch Hancox (Macclesfield Town) is shown the yellow card for a bad foul.
Marvin Johnson (Oxford United) wins a free kick on the left wing.
Foul by Mitch Hancox (Macclesfield Town).
Attempt saved. Paul Lewis (Macclesfield Town) left footed shot from the centre of the box is saved in the centre of the goal. Assisted by Danny M. Rowe.
Corner,  Oxford United. Conceded by Mitch Hancox.
Offside, Macclesfield Town. Andy Halls tries a through ball, but John McCombe is caught offside.
Foul by Tyler Roberts (Oxford United).
Danny Whitaker (Macclesfield Town) wins a free kick in the attacking half.
Attempt missed. Ryan Taylor (Oxford United) right footed shot from the centre of the box misses to the right. Assisted by Chris Maguire following a corner.
Attempt missed. Chris Maguire (Oxford United) right footed shot from outside the box misses to the left. Assisted by Cheyenne Dunkley following a corner.
Corner,  Oxford United. Conceded by Craig Ross.
Attempt saved. Tyler Roberts (Oxford United) left footed shot from the centre of the box is saved in the bottom left corner.
Attempt blocked. Alexander MacDonald (Oxford United) left footed shot from the centre of the box is blocked. Assisted by Marvin Johnson.
Attempt saved. Danny Whitaker (Macclesfield Town) right footed shot from outside the box is saved in the top centre of the goal. Assisted by Paul Lewis.
Cheyenne Dunkley (Oxford United) hits the right post with a header from the right side of the box. Assisted by Chris Maguire following a set piece situation.
Tyler Roberts (Oxford United) wins a free kick in the attacking half.
Foul by Mitch Hancox (Macclesfield Town).
Attempt blocked. Chris Maguire (Oxford United) left footed shot from the right side of the box is blocked. Assisted by Philip Edwards.
Substitution, Oxford United. Ryan Taylor replaces Joe Rothwell.
Attempt missed. John McCombe (Macclesfield Town) header from the centre of the box is too high. Assisted by Danny M. Rowe with a cross following a corner.
Corner,  Macclesfield Town. Conceded by Cheyenne Dunkley.
Offside, Macclesfield Town. Paul Lewis tries a through ball, but Danny Whitaker is caught offside.
Marvin Johnson (Oxford United) is shown the yellow card.
Corner,  Macclesfield Town. Conceded by Simon Eastwood.
Attempt missed. Chris Maguire (Oxford United) right footed shot from outside the box misses to the left. Assisted by Tyler Roberts.
Offside, Macclesfield Town. Andy Halls tries a through ball, but Chris Holroyd is caught offside.
Corner,  Macclesfield Town. Conceded by Marvin Johnson.
Attempt missed. Ryan Ledson (Oxford United) right footed shot from more than 35 yards misses to the left. Assisted by Chris Maguire.
League One side Oxford United twice hit the woodwork as they were held to a goalless FA Cup second-round draw at Macclesfield.