A preliminary police estimate put the crowd at 130,000, but organisers said half a million people took part.
The march came at the end of a weeklong series of demonstrations led by a former ally of the president who said he was fed up with the culture of corruption that has flourished in Taiwan under Chen Shui-bian's leadership.
Since last weekend, protesters have maintained a vigil outside the ornate Presidential Office building, chanting slogans and giving their trademark "thumbs down" sign over allegations that people close to Chen - including his wife and son-in-law - used their proximity to him for personal financial gain.
Friday's march took place in driving rain as Typhoon Shanshan skirted the eastern Taiwanese coast.
But that didn't appear to affect the mood of the marchers, many of whom were dressed in red to symbolise their anger with Chen's leadership.
Some of the demonstrators held black-rimmed portraits of Chen, characteristic of Taiwanese funeral processions.
Others clutched red signs, bearing the Chinese characters for "Taiwan's shame" and "End corruption now", as drums beat rhythmically in the background.
For the past six months Chen has been on the defensive over a series of high-profile corruption scandals.
Earlier this month the presidential office acknowledged that prosecutors questioned Chen himself about the use of false invoices to account for part of a secret fund used to sustain Taiwanese diplomatic activities abroad.
Chen denied any wrongdoing in the affair, and insisted he will stay on until the end of his term, which ends in May 2008.
Shih Ming-teh, the former chairman of Chen's ruling Democratic Progressive Party, has been leading the anti-Chen effort, leveraging his moral authority as a veteran campaigner against Taiwan's now deposed martial law regime to press for a new era of corruption-free politics on this island of 23 million people.
Shih said: "Our leader has made grave errors. That's why we have to be here in this terrible weather."
Shih has vowed to continue his efforts until Chen resigns, though it may be difficult to sustain the momentum of the past week, especially with the legislature resuming work on September 19 after its summer recess.