The midfielder suffered knee ligament damage in last weekend's 2-0 defeat to West Ham United at the London Stadium.
Newcastle issued a statement saying that it was "likely" that Longstaff would miss the rest of the campaign.
And Benitez hopes that the 21-year-old will be fit in around three months.
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“When you have an injury in team, it's bad news," said manager Benitez. "When you have a young player doing so well, it's worse.
"Talking with him, he's fine, mentally. He's strong enough. It happens in football, and he said ‘now I have to start working’. His reaction has been positive. We're really disappointed, but he has taken it really well in terms of his approach.
“It's a serious injury, but so serious. Now with modern techniques, it’s fine. You saw with (Florian) Lejeune how he recovered.
“This is a knee also, damage of the crucial ligament, but not as bad as others.
“I don’t think he will have time this year to be ready. Mentally, he's fine, and in two or three months he will be ready again."
Longstaff, promoted to the first-team squad last summer by Benitez, had started 11 consecutive games for United.
“The staff were talking the other day, I was answering this question about how he was doing well training, and nobody could have seen he would have settled so quickly and been a key player for us," said Benitez.
"Hopefully, he will be fine for us and in the future.
“The environment around him is fine. They (his family) will keep him calm, and he will get good advice.
“He's done really well, I don’t think he will have time this year, but I think he will be fine. We knew right away after the game it was quite serious, but the good news is that it’s not as bad as it could be."