The England Under-21 boss was himself sacked by Boro chairman Steve Gibson in 2009 and now Mowbray has been shown the door after a poor run of results culminating in a 3-2 loss at Barnsley.
Southgate told Sky Sports News: "I was at the game at the weekend and was aware of the reaction of the supporters - that always makes things difficult for a manager.
"It is a great shame for Tony because nobody would have been prouder to manage Middlesbrough than him.
"In a similar way to myself there, results dictate and, ultimately, I am sure it would have been a difficult decision for the chairman to take because he respected Tony enormously."
Meanwhile, speaking to Sky Sports News Radio, former Middlesbrough favourite Bernie Slaven feels Mowbray was let down by those above him.
"He is a great man of principle, I played alongside him and he was a great captain and leader, but since the turn of the year five paltry wins, I say this morning it is with regret - Mogga has had a tough old time but I don't think since he took the job he has had a full time backing," Slaven said.
"His first two years was about cost cutting to keep the guys above him happy, and he never had the full backing for me.
"It is the manager who carries the can, but whoever takes the job, one change isn't going to change our fortunes - we still have the same players, we still have the same financial restraints, we still have the same chairman and we still have the same dwindling crowds."
Slaven feels getting the crowd back on side is a major concern for the club and he feels appointing Martin O'Neill would be the right course of action.
"The crowd is a massive concern, how do you get them back? If I had a choice, I know he failed at Sunderland, I would go for Martin O'Neill - he has got the X-Factor for me."
Gareth Southgate is an ambassador for the StreetGames Football Pools Fives, a programme taking football to thousands of disadvantaged young people across the UK.