Oxford leapfrogged Macclesfield in the table as goals from Simon Heslop and James Constable fired them to their third straight win in front of their biggest crowd of the season.
Substitute Ricky Sappleton pulled a goal back for Town but it was mere consolation as the Us held on to win 2-1.
Playing for the first time since Dec 4, Oxford looked rusty at times but Heslop settled them down by drilling in a right-foot shot after 17 minutes after good work by Constable and Steve MacLean.
Macclesfield were a threat and Colin Daniel had an 18-yard effort saved before Tyrone Barnett headed over and Constable cleared off his own line at the start of the second half.
The Us gave themselves a two-goal cushion in the 70th minute when Heslop`s shot hit a defender and fell kindly for Constable to smash home his 10th goal of the season.
Further Oxford goals might have followed but Jose Veiga saved from Asa Hall and MacLean before Sappleton set up a tense finale with a tidy close-range finish.