Red Nose Day organisers are hoping the charity appeal will remain "recession proof" as it marks its 25th anniversary.
Music mogul Simon Cowell is to appear on this year's telethon on March 15 in a sketch in which he will get married, while Rowan Atkinson will showcase his latest character as the Archbishop of Canterbury.
Emma Freud, director of Red Nose Day, said: "I think 25 years in, it will be the best TV show we've ever done. I can confidently say that. It amazes me that it has gone as long as it has and it's remained as popular as it has.
"I think Red Nose Day used to be something that a group of comedians organised and tried to galvanise the country into doing something for the developing world. Now it's sort of owned by the general public. It's something pretty much every school in the country says, 'it's Red Nose Day, what are we going to do?'."
Henry, 54, was dressed in a bright red suit as he joined presenters Dermot O'Leary, Claudia Winkleman, Helen Skelton and Kate Thornton, along with comic stars David Baddiel, Frank Skinner, Jimmy Carr and Ben Miller at the Royal Festival Hall in central London.
The Red Nose Day appeals have raised some £800 million since launching on February 5, 1988. Organisers believe the British public has become "more empathetic" despite the recession after Comic Relief raised a record total two years ago.
Ms Freud added: "I don't know if we're recession proof. I think this is going to be quite an interesting year to watch.
"Two years ago, when we were a year into the recession, we absolutely expected our money to take a downturn. People were really strapped for cash and it was all anybody was talking about. But two years ago we made £22 million more than we'd ever made before. We took £108 million on Red Nose Day. It was our greatest year ever."