Kion Etete gave the Cobblers a sixth-minute lead before Sam Smith leveled a short time later.
The result means a replay will occur in ten days time at the Abbey Stadium.
Story of the match
The hosts were ahead after just six minutes when a long pass by Sam Hoskins was brought down by Etete and he slid his shot under Dimitar Mitov.
He nearly doubled the Cobblers' lead minutes later, but the Cambridge defense cleared after the striker slipped.
The U's levelled the scoring when Shilow Tracey drew a foul just outside of the area and the ensuing free-kick by Jack Iredale was headed home by Smith.
It was end-to-end action and former Cambridge man Paul Lewis headed over the bar while at the other end, Paul Digby did the same.
Ben Worman was only denied by a brilliant block by Dominic Revan and Liam Roberts denied Joe Ironside's acrobatic effort.
Three minutes later, the hosts regained the lead as Etete raced down the byline and squared for Lewis, who scored into the empty net.
In the 55th minute, Smith came close to doubling his tally as he sent a shot over the bar and sent another chance wide.
Hoskins looked to double the Cobblers' lead, but some last-ditch defending by the U's denied him from ten yards out.
Harvey Knibbs came on to replace Worman and he had an immediate impact, winning a free-kick that Masterson fired home from inside a crowded six-yard box.
Both teams pushed for a winner and Mitov denied Mitch Pinnock twice while a Jensen Weir cross was volleyed just over the crossbar by George Williams.
Man of the match: Conor Masterson
In a match with little in it, his goal kept Cambridge alive in the competition, showing excellent composure to score amongst a crowd of players.