A brace of tries from George McGuigan and Sean Robinson snapped Newcastle's six-match losing streak as they swept London Irish aside with a dazzling second-half display.
The Falcons twice came from behind as Louis Schreuder scored his first Newcastle try and Sean Robinson, Ben Stevenson and Tom Penny also went over.
Brett Connon's 40-yard penalty closed out the win.
Irish had led 15-14 at half-time but fell apart after the interval.
The visitors applied the early pressure and opened the scoring in the seventh minute when scrum-half Nick Phipps switched play to the left flank, with Tom Parton bursting through to cross the line.
However, the Falcons weathered the storm and fought back, with the visitors conceding a string of penalties and Schreuder's quickly-taken tap opened up space for McGuigan to crash over.
Connon's first conversion of seven edged Newcastle ahead and they stretched that lead when a clever move from the lineout paved the way for a rolling maul that enabled Robinson to make it 14-5.
The Exiles' response was immediate, with Paddy Jackson slotting a penalty before unfurling a perfectly-judged grubber kick that was gobbled up by Ben Loader and the winger raced over in the corner to restore his side's advantage on the stroke of half-time.
The topsy-turvy scoring pattern continued when the teams turned around, with Callum Chick slipping through the Irish defensive line and offloading with the back of his hand for Schreuder to touch down.
Curtis Rona's high challenge on Matias Orlando then earned him a yellow card and Newcastle took advantage to score two quick tries through McGuigan and Stevenson.
With Irish still a man short, centre Phil Cokanasiga pulled a try back and Newcastle's success was by no means assured when Ben Donnell offloaded for Motu Matu'u to narrow the gap to 11 points.
But Jackson's conversion rebounded off the post and the Falcons sealed their triumph - topping the 50-point mark for the first time this season - as Mark Wilson set up Penny to score in the corner and Robinson added his second of the game.
Newcastle director of rugby Dean Richards said:
"We didn't start the game well, but we gradually took control. We could've seen heads drop going into half-time having just conceded, but the boys responded.
"We were a transformed side in the second half. We just wanted to play in a relentless way whereby we didn't take a backwards step, and the introduction of the bench made a big impact as well.
"We are looking forward to building on this performance and we start with hosting Northampton a week on Monday. It will give the players a huge boost knowing that there is going to be fans at the ground."
London Irish director of rugby Declan Kidney said:
"The most frustrating thing about today is knowing how good we actually are. We did okay for the first 15 minutes and worked our way back into the lead at half-time, but we're playing short of our potential at the minute.
"Newcastle were fully deserving of the victory and the margin of it as well. There are some things that I can congratulate them on and then there are other things that we need to start executing better.
"Little moments changed the game and when you concede 14 penalties then it will make things more challenging. Missing a conversion and the wind picking up all came back to bite us."
Newcastle Falcons: Penny; Radwan, Orlando, Burrell, Stevenson; Connon, Schreuder; Davison, McGuigan, Mulipola, Peterson, Robinson, Welch, Wilson, Chick.
Replacements: Blamire, Cooper, Tampin, Van der Walt, Fearns, Stuart, Hodgson, Wacokecoke.
London Irish: Parton; Loader, Rona, Cokanasiga, Hassell-Collins; Jackson, Phipps; Goodrick-Clarke, Creevy, Chawatama, Nott, Simmons, Rogerson, Cowan, Tuisue.
Replacements: Matu'u, Gigena, Hoskins, Munga, Donnell, Groom, Atkins, Stokes.
Referee: Jack Makepeace