Winger Duane Holmes had headed them ahead in the 35th minute with his third goal of the season.
He found himself in the box to meet a right wing cross from Josh Morris and tuck his header just inside the far post.
It came just after Oxford had threatened to snatch the lead when Chris Maguire fired a free-kick from the edge of the box over the defensive wall to force a flying save from goalkeeper Luke Daniels.
Swirling mist made it difficult for spectators to follow some of the play.
It was Oxford who made a storming start to the second half and were deservedly back on level terms in the 47th minute.
From a right wing corner the ball was played into a crowded box by Alex MacDonald and turned home from close range by defender Phil Edwards.
It was the first goal conceded by Scunthorpe in four games and suddenly they were under pressure.
There was relief in the home defence when Kane Hemmings failed to capitalise on a left wing cross in front of goal.
Twice though Scunthorpe did go close to snatching a winner, as first striker Kevin Van Veen glanced a header just wide of the far post from Morris' in-swinging free-kick.
Then substitute Jamie Ness let fly with a shot from the edge of the box that whistled just inches wide before Scunthorpe finally had to settle for a point to break that previous unbeaten home record which had stood for 65 years.