Brown will miss Premier League games against Fulham, Liverpool, Bolton and a potential title-decider against Chelsea on April 3. The injury will also rule him out of the Champions League quarter-finals were United to progress.
Brown, who also broke a metatarsal bone just over a year ago, would then almost certainly be absent for the games with Blackburn on April 11 and against derby rivals Manchester City a week later.
"It's just unfortunate," United manager Sir Alex Ferguson admitted.
"He has had a career blighted by injury and they've all been long ones, and now he has another. He'll be out for four to six weeks.
"I hope to get him back for some of the season."
Brown picked up the injury during United's 1-0 win over Wolves on Saturday in a challenge with Matt Jarvis, and left Molineux with a protective boot on the damaged foot.
The recovery timescale is at least good news for England, with Brown expected to be part of Fabio Capello's squad for the World Cup after playing at right-back against Egypt last week.
Brown's absence further adds to Ferguson's woes ahead of tomorrow night's crucial European encounter against Milan, which will see United defending a 3-2 advantage from the first leg at the San Siro.
Anderson (knee), Ryan Giggs (arm) and John O'Shea (leg) are also out, although Ferguson confirmed the in-form Wayne Rooney would be available after a knee problem.
"He is fit," Ferguson said of the England frontman.
"There is a rapid improvement from Saturday morning because on Friday evening I didn't think he had any chance.
"It's good news. He is a threat to anyone at the moment."