Harry Maguire joined Manchester United for £80m from Leicester in August 2019
Maguire, 30, gained his 59th cap but scored an own goal in the 3-1 away friendly win over Scotland on Tuesday.
He helped England reach the 2018 World Cup semi-finals and the final of Euro 2020, but has struggled for first-team football at Manchester United.
"I've never known a player treated the way he is," said Southgate.
"He's been an absolute stalwart for us in the second most successful England team for decades - he's been an absolutely key part of that.
"I've talked about the importance of our senior players, he's been crucial among that.
"Every time he goes on the field, the resilience he shows is absolutely incredible. He's a top player and we're all with him and our fans were brilliant with him."
Maguire was stripped of the United captaincy this summer and linked with a move away from the club, but remained at Old Trafford after injuries to fellow defenders.
He made his first appearance of the season on 3 September as a second-half substitute in United's 3-1 loss to Arsenal.
Against Scotland, Maguire came on as a substitute at half-time and was mocked by the home fans before he scored a 67th-minute own goal.
"From a Scotland fans' point of view I get it. I have absolutely no complaints with what they did," added Southgate.
"But it's a consequence of ridiculous treatment of him for a long period of time.
"It's a joke. Not by the Scottish fans but by our own commentators, pundits or whatever it is. They've created something that's beyond anything I have ever seen.
"I think our fans recognised, 'OK there might be a bit of heat from our own supporters but we're not going to have others getting into him'."
Harry Maguire has played more minutes for England this season than he has for his club Manchester United
Former England winger Chris Waddle, speaking on BBC Radio 5 Live, agreed that Maguire was being targeted unfairly.
"Give him credit, I didn't see him give the ball away, the own goal was the only thing he did wrong," said Waddle.
"He should've gone abroad and got a move. If he had gone to Italy he could pass the ball out from the back - we know he lacks a bit of pace.
"It would've been ideal to go abroad and play football for a year then when he comes back to England he would get half [of the criticism] he gets now and it's ridiculous what [criticism] he gets now."
Maguire ended the game with the England captain's armband after Harry Kane, who had scored England's third goal after earlier strikes from Phil Foden and Jude Bellingham, was substituted in the 84th minute.
Southgate again praised Maguire's character for how he reacted after the game.
"He's gone and spoken to the media as that's the sort of lad he is," added Southgate. "He's fronted up as he always does, again enormous credit to his character.
"He's great, we've had a big win. He's been a big part of that."
-- Courtesy of BBC Sport