Fit-again Yohan Cabaye had given the Magpies a deserved lead at a snow-swept St James' Park with a curling free-kick on the half-hour mark.
The hosts could have been further ahead but for some superb stops by Adam Federici.
Twice the Australian denied Papiss Cisse from point-blank range, brilliantly tipping a header around the post before throwing himself in front of the striker to keep out a volley.
And Le Fondre made sure Federici's heroics were not in vain, with his introduction again proving the catalyst for a dramatic Royals comeback.
The £300,000 Rotherham United signing had barely been on the pitch a minute when he bundled home Jimmy Kebe's cross midway through the second half.
Just five minutes later he further enhanced his supersub status by neatly finishing past Tim Krul after Hope Akpan scuffed his shot on the edge of the box.
The quickfire double took Le Fondre's goal tally to 10 for the season in all competitions, with eight in the Premier League.
But manager Brian McDermott says there is no guarantee that goals alone will be enough to earn him a starting spot.
"I talk to Adam and it's difficult, I have to do whatever I think I can to get a result, and if he has to come off the bench and get the winning goal he is going to be the hero," explained McDermott.
"Sometimes games are different, you can play 4-4-2 from the start and change things around but in this division you can't get knocked down too early. That has been happening to us too many times recently.
"You know what you are going to get with Alfie, you know he is going to get a chance to score, that is what he does.
"He wants to play but we have to get results and do whatever it takes."
Along with Le Fondre, McDermott also had praise for the 1,000 fans who made the long journey up to a bitterly cold St James' Park.
Some supporters took 12 hours to reach the North East after a number of flights were cancelled.
Even the Royals squad itself had to travel up by coach after its own flight was grounded due to the snow. But the trip was well worth the effort for all concerned as Royals chalked up their first away win of the season to further boost their chances of avoiding the drop.
"I cannot believe how many people turned up, I was shocked," admitted McDermott afterwards.
"The best part for me was to go those fans at the end, I hope they enjoyed themselves."
The victory lifted Royals briefly out of the bottom three on goal difference but Aston Villa's draw at West Brom in the evening kick-off sent McDermott's men back into the relegation zone.
Up next for Royals is Sheffield United in the FA Cup this Saturday (3pm ko) at the Madejski before another home Premier League game against Chelsea on Wednesday, January 30 (8pm ko).
Newcastle: Krul - Debuchy, Williamson, Coloccini, Santon - Anita (Obertan 80), Cabaye (Bigirimana 74), Shola Ameobi, Marveaux (Perch 65), Gutierrez - Cisse. Unused subs: Elliot, S.Taylor, Sammy Ameobi, Ranger. Booked: Williamson, Debuchy.
Reading: Federici - Harte, Kelly, Pearce, Mariappa - Leigertwood, Guthrie (Le Fondre 70), McAnuff, McCleary (Akpan 64), Kebe - Pogrebnyak. Unused subs: Taylor, Gunter, Morrison, Karacan, Hunt Booked: Kelly, Guthrie, Kebe.
Attendance: 49, 411.
Referee: Andre Marriner (West Midlands).