Erik ten Hag had decided to send on Fred and Anthony Martial before Tottenham scored in their draw with Manchester United.
Ten Hag replaced Christian Eriksen and goalscorer Jadon Sancho in the 61st minute - five minutes after Spurs wing-back Pedro Porro scored to make it 2-1.
Eriksen had excelled in midfield and Sancho enjoyed arguably his finest performance of the season before their removals. Ten Hag then sent on Wout Weghorst and Tyrell Malacia for Antony and Aaron Wan-Bissaka in the 71st minute.
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Malacia was caught out for Son Heung-min's equaliser in the 79th minute as United threw away a 2-0 interval advantage to draw 2-2 for the second time this month.
Ten Hag's changes in the draws with Spurs and Sevilla, as well as the defeat at Newcastle on April 2, have drawn criticism but he defended his in-game management.
"If you have seen the game you have seen also in the period after half time we lose control in the game," Ten Hag explained, "and I prepared the subs already before the 2-1 and you could see that goal coming.
"With Fred, you bring energy, one who can win the ball. On Sunday he was brilliant. And with Martial, you bring one who can keep the ball and you can have (Marcus) Rashy, Antony and Bruno (Fernandes) make runs behind and that was the idea."
Ten Hag acknowledged United excelled in phases during the first half when Sancho and Rashford scored from similar areas. "It has to do with awareness - where's the free men?
"Before half-time, we had an overload in the midfield and we used it very well, especially with the switches from right to left. I think Spurs had huge problems with that. We scored the goals with passes from right to left.
"After half time, it was different because we couldn't keep the ball and we lose control."
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