James Wesolowski's second goal for the club was enough to seal Accies second win in four days and take them 11 points clear of rock-bottom Falkirk.
Flavio Paixao went close to doubling the advantage and was also denied what appeared a clear-cut penalty as the visitors' top-six hopes suffered another huge blow.
Mark Connolly, 18, made his professional debut in one of two changes for the visitors, who also recalled the fit-again Kenny Deuchar.
Accies named the same side for the third straight match following Wednesday night's win at Kilmarnock.
Saints were returning to the scene of their first SPL victory since promotion, Derek McInnes' men having won 2-0 at New Douglas Park in October.
And the visitors went close to a fourth-minute opener when Filipe Morais' knockdown from Danny Grainger's free-kick was deflected just past the post for a corner.
Five minutes later, Jody Morris stung the palms of Tomas Cerny from 20 yards but Hamilton immediately broke down the right, Mickael Antoine-Curier heading Dougie Imrie's far-post cross wide under pressure.
Antoine-Curier was also off target with a more difficult header midway through the half.
Deuchar and Martin Canning were briefly forced from the field following a clash of heads.
Simon Mensing blasted a 28th-minute free-kick straight at the wall and, as the ball was sent back into the box, Antoine-Curier wasted a great chance, failing to connect as it found its way through to the big striker.
Accies briefly began to motor but the game soon became fractious once more and Connolly earned himself a debut booking after clattering into Flavio Paixao on the touchline.
Michael Duberry quickly followed suit for a foul on the same player on the opposite side of the pitch.
A brief shoving match erupted after which James McArthur also saw yellow.
The first half looked destined to end goalless until two minutes from the break when Simon Mensing fed Wesolowski on the edge of the box and the Australian was given enough time by a static Saints defence to fire the ball into the corner of the net.
The second half was preceded by a stadium announcement asking Deuchar's father - who like his son is a doctor - to report to the tunnel.
Deuchar did not emerge with his Saints team-mates due to concussion and was one of two half-time substitutions as Connolly also left the field and Collin Samuel and Steven Anderson came on.
The changes reinvigorated the visitors somewhat, but they were unable to seriously test Cerny until just past the hour mark when Hamilton failed to deal with Gary Mackay's long ball and Liam Craig saw his shot turned behind.
Anderson then headed Morais' wicked corner wide after the ball evaded everyone else in the box.
Joel Thomas came on for Antoine-Curier in the 66th minute, three minutes before Paixao was denied by a wonderful save from Graeme Smith, who somehow clawed the Portuguese's header from Mensing's cross over the bar.
Paixao then produced a moment of outrageous skill that should have earned Hamilton a penalty.
The forward turned and flicked the ball over Anderson's head in one motion before being hauled back by the defender.
Incredibly, referee Crawford Allan waved play on.
The next goal looked like coming from Accies and a clever free-kick routine ended with Thomas volleying acrobatically over the bar.
Saints threw on Sheridan for Murray Davidson for the final 10 minutes.
As they pushed forward, they found themselves being caught on the break and McArthur went close with a 30-yard piledriver.
Marco Paixao replaced Imrie as Hamilton ran down the clock, though there was still time for Morris and Grainger to be booked before the final whistle and Craig after it as tempers flared.