The Victoria Park outfit had lost to Cambridge by the same scoreline in the reverse fixture, but a fourth victory in a row sees Hartlepool get their head above water for the first time in five months.
Brad Walker headed the hosts in front in the 20th minute, before Matt Harrold's left-footed strike restored parity 12 minutes later.
Ronnie Moore's men refused to give up on the three points, though, and eventually found a winner when Scott Harrison fired into the top left-hand corner after 67 minutes.
The result pulls Tranmere Rovers - Moore's former club - back into the danger zone following their 1-1 draw at home to AFC Wimbledon.
Tranmere looked set to end the match empty-handed until George Green fired in an equaliser in the fourth minute of stoppage time.
Cheltenham Town go bottom following their morale-sapping 3-0 home defeat at the hands of Plymouth Argyle.
York City gave themselves some breathing space with a 4-1 win at Mansfield Town, despite having goalkeeper Robert Olejnik sent off shortly after the half-hour.
Russ Wilcox's men move four points clear of the relegation zone, ahead of Carlisle United - 2-1 losers at Oxford United with Troy Archibald-Henville sent off - on goal difference.
At the top of the table, Shrewsbury Town and Wycombe Wanderers closed the gap on leaders Burton Albion to two points with 2-0 and 1-0 wins at Portsmouth and Dagenham and Redbridge respectively.
Burton host Stevenage on Monday.
In the day's remaining fixtures, Luton Town slipped out of the play-off positions at Plymouth's expense courtesy of a 2-1 loss at Northampton Town, Exeter City drew 1-1 with Morecambe, and Bury's clash with Southend United was abandoned after six minutes due to a waterlogged pitch.
