Two key allies of President Hosni Mubarak, including his son Gamal, were stripped of their posts.
Hossam Badrawi, a reformer and top physician, took both positions.
US special envoy Frank Wisner welcomed the resignations and said President Mubarak should stay in power to steer the transition.
Protesters still occupy Cairo's Tahrir Square, but their numbers have fallen from Friday's huge rally.
President Mubarak has also held talks with his ministers to try to revive the economy.
Banks will reopen on Sunday, but Finance Minister Samir Radwan said the economic situation was "very serious".
Analysts say the uprising is costing the country at least $310m a day.
Safwat Sharif has been a major figure in Mr Mubarak's power structure for a long time. He is, I think I can say, fairly well hated by a lot of people including everybody in the square behind me.
Gamal Mubarak was until relatively recently apparently being groomed to succeed his father as president. Well obviously that's not going to happen.
As the news came through I was down among the crowd, and they saw this as another concession. They said they were getting concessions every day now. I think it will encourage them to keep going for the big prize they insist they must have, and that is for Mr Mubarak himself to go.
Earlier there were reports of an explosion at a pipeline that supplies gas to Israel and Jordan. The blast caused a fire near el-Arish, Egyptian state television reported.Elite in turmoil
The resignation of leading NDP officials was announced on state TV.
"The members of the executive committee resigned from their posts. It was decided to name Hossam Badrawi secretary general of the party," it said.
Gamal Mubarak lost his post as head of the policies committee, along with Secretary-General Safwat al-Sharif.
A state-owned TV report said President Mubarak, as party leader, had accepted the resignations.
An earlier report from a private TV channel said President Mubarak had also given up his party post, but this was later retracted.
US special envoy Frank Wisner said Gamal Mubarak's resignation was a positive step.
"There is a chance to move forward. It's fragile, it's the first stage, things could go wrong. But the direction is promising," he said.
The US was looking forward to additional steps towards political change, he added.
The BBC's John Leyne in Cairo says that while the new secretary-general, Dr Badrawi, is seen as a liberal he is still close to the ruling family, and this is another indication of the turmoil in the ruling elite.
Mr Mubarak has already aid he will not stand for re-election as Egypt's president in September, but insists he must stay until then to prevent chaos in the country. Protesters are demanding that he goes immediately.Huge impact
On Saturday, the president met the prime minister, finance minister, oil minister and trade and industry minister, along with the central bank governor.
Trade Minister Samiha Fawzi Ibrahim said exports were down 6% in January and that the authorities were providing extra food to try to stabilise prices and curb shortages.
Banks and the stock exchange have been closed for days, and many factories in the major cities have shut.
State media said the stock market would not now open on Monday as planned.
The BBC's Kevin Connolly, in Cairo, says the paralysis induced by the protests is having a huge impact on the creaking economy. Tourists have been frightened away and the prices of basic goods like cigarettes and bread have been soaring.
He says many Egyptians are beginning to wonder aloud how quickly daily life will return to normal regardless of the outcome of the struggle for power.
Speaking to the BBC, Mr Radwan admitted the economy faced a "very serious" situation and that he was in constant touch with the International Monetary Fund and the World Bank.
But he also said the economy had a "solid base" and "so far, we are coping".
Economists at Credit Agricole say the uprising is costing the country at least $310m (£192m) a day and they have revised down their economic growth estimate for Egypt this year from 5.3% to 3.7%.
Mr Radwan also said there would be a meeting with opposition groups to try to end the 12 days of protests.
He said Vice-President Omar Suleiman and "almost certainly Prime Minister Ahmed Shafiq" would attend, adding that they would have "sufficient authority to negotiate with the opposition".
He did not say which opposition groups would attend. Egyptian television said the al-Wafd and al-Tajammu parties would be at the talks.
The biggest opposition group in Egypt, the Muslim Brotherhood, has said it will take part in discussions provided the government submits political reform within a specified time frame. But it also insists Mr Mubarak must leave office immediately.
It also reported that the curfew had now been shortened and would be in effect from 1900 to 0600 local time (1700-0400 GMT).
On Saturday at a conference in Munich, US Secretary of State Hillary Clinton said the "status quo" of undemocratic nations in the region was "simply not sustainable".
She said: "Governments who consistently deny people freedom will open the door to instability... free people govern themselves best."
The UN believes more than 300 have died across Egypt since the protests began on 25 January, with about 4,000 hurt.