Reverse singles are Sunday, along with a possible deciding doubles match.
The United States, playing without the injured Williams sisters, has been the Fed Cup runner-up the past two years. Belgium would have been an even bigger favorite this week had Justine Henin not suddenly retired last week.
The Belgians will get plenty of crowd support at the Sports Palace, which is expected to top 10,000.
"This will be the biggest crowd we have played against the last couple of years," U.S. team captain Mary Joe Fernandez said. "It is great for Fed Cup. It is great for both teams. We are going to pretend they are rooting for us the whole time."
The U.S. team is accustomed to playing without the Williams sisters. Venus is sidelined with a groin injury sustained at the Australian Open, and Serena has been out since Wimbledon of last year because of a foot injury.
"It's a matter of playing your best whenever you play and approaching it the right way," Fernandez said.
The combination of Mattek-Sands, ranked 48th, and Oudin (No. 61) should be no match for second-ranked Clijsters and 26th-ranked Wickmayer. But Fernandez is hoping that her team reaches the doubles on Sunday.
"I have always said I want it to come down to the doubles," Fernandez said. "That's always my goal. If we win before that, it is a bonus, but we like our chances if we get down to the doubles."
South African-born Liezel Huber is 3-0 in deciding doubles matches for the United States. Mattek-Sands hit her groove early this season, helping the U.S. mixed team win the Hopman Cup.
The U.S. hasn't won the Fed Cup since 2000, when it defeated Spain. It has never lost consecutive Fed Cup matches. Belgium won its only Fed Cup in 2001, when Clijsters was a young player on the team.