Williams has been stuck on 21 since winning Wimbledon last summer and fell just short again at the French Open on Saturday with a 7-5 6-4 final defeat by Garbine Muguruza.
In the last three slams, Williams has lost once in the semi-finals and twice in the final, and Mouratoglou feels history is weighing heavily on her.
The Frenchman, Williams’ coach since 2012, said: “There is a very high level of expectation and tension on this 22nd grand slam. It doesn’t make her play badly but maybe not aggressively enough to win it.
“This 22nd is difficult, but the 17th and 18th [when Williams was looking to equal Chris Evert and Martina Navratilova] were difficult, too. It’s normal. You cannot play a grand slam final for history the same way as any other.
“It’s going to take the time that it’s going to take but we’re going to do it, we’re going to make it.”
Mouratoglou had said before the match that it was on Williams’ racket, a comment that may well have provided the powerful Muguruza with a little extra motivation.
He stuck to his guns but said the Spaniard surprised him with the confident way in which she finished the match, serving out to love after Williams had saved four match points. He added: “She deserves 100 per cent to be a grand slam champion because, when you’re able to be hitting every shot to win, it’s something that a lot of players even who’ve been number one were not able to do in grand slams.”