With his team trailing by 10 points in the fourth quarter, Brady came alive to deliver two drives which both resulted in touchdowns late on, with wide receiver Julian Edelman catching the winning pass.
Seattle had a chance to nick a late win, but a dramatic interception in the red zone from rookie cornerback Malcolm Butler ended their hopes and secured victory for New England.
Brady and his side have now won four Super Bowls, and he had to work hard to see off the defending champions in a end-to-end encounter.
After a lengthy opening drive from the Patriots, Brady tried to fire the ball into the endzone, but his pass was intercepted by Jeremy Lane.
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The Seahawks cornerback looked to run his first career pick back for the defending champions, but a tackle from Edelman forced him out of the game with an arm injury.
The AFC champions finally opened the scoring early in the second quarter when Brady managed to connect with his receivers, using Edelman to move the ball to the 10-yard line before Brandon LaFell hauled in the touchdown catch.
Russell Wilson struggled to get the Seattle passing game going, but eventually found Chris Matthews for the receiver's first career reception, before Marshawn Lynch powered over to level the scores with just over two minutes to play.
The Patriots had a chance to restore the lead just before the break as Brady got the ball back, and he eventually managed to pick out Rob Gronkowski, leaving the tight end to hold off coverage from KJ Wright and haul the ball in in the corner of the endzone.
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The NFC champions had time to get the ball back downfield with just over 30 seconds left on the clock, and with moments remaining, Wilson threw a bullet to Matthews to draw the Seahawks level again having turned down the safe option of a field goal.
After the break, Wilson again connected with Matthews on a long pass as the Seahawks set up an early red zone attack, but they couldn't turn it into a touchdown. However, Steven Hauschka kicked a field goal to give his side the lead for the first time in the match.
Brady then threw a second pick of the match, this time by Bobby Wagner making the interception, before Wilson found Matthews for the third time with a long pass.
That set up their third touchdown of the night as Wilson found wide receiver Doug Baldwin, who took a simple catch after he cleverly lost his marker in a congested endzone.
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The Patriots entered the final quarter 24-14 behind, but they closed the gap to three points midway through when Brady found Danny Amendola from close range.
The Seahawks failed to keep hold of the ball for long when they were next in possession, and Brady had a chance to steer his side into the lead.
He duly obliged when he connected with Edelman with just two minutes to go, as the wide receiver cut back inside his man to grab the ball at the front of the endzone.
In response, the Seahawks fought gallantly and made it to within a metre of the endzone, but Wilson opted to pass instead of hand it to Lynch.
Butler intercepted the ball on the edge of the endzone, ending Seattle's hopes of back-to-back Super Bowl titles.