Gates, speaking in an interview with AFP during a visit to Ghana, fended off criticism from those who have argued that the effort and money could be better spent on other causes, arguing forcefully against a reversal of course.
The number of worldwide polio infections was down to 223 in 2012 compared to 360,000 in 1988, when the United Nations launched a campaign to eliminate the highly contagious and crippling illness.
"Just to contain it to say 100,000 (cases) a year, you're going to be spending a lot of money," said the Microsoft co-founder listed by Forbes as the world's second-richest as well as its most generous person.
"And so anyone who thinks that giving up on polio saves money, you don't save money," Gates added, with the interview also falling on the 60th anniversary of Jonas Salk's announcement of a successful test of a polio vaccine.
Only three countries are still considered polio endemic -- Nigeria, Afghanistan and Pakistan -- and Gates' foundation has been on a high-profile campaign to eradicate it.
Nigeria, where an Islamist insurgency in the country's north has taken a hit on immunisation campaigns and at least 10 people were killed in attacks on two vaccination centres in February, saw most of the cases in 2012.
At least 20 people have been killed in such attacks in Pakistan since December.
Gates said the global campaign to eliminate polio was currently spending about $900 million a year, with a new six-year plan to eliminate the disease to be discussed at a Global Vaccine Summit in Abu Dhabi on April 24 and 25.
"If you just want to go into the 'keep it to 100,000 (cases)' mode, you could probably drop down to $500 million a year," Gates said.
"But then you'll be spending $500 million for the rest of time instead of spending $900 million for six years, and you'll have 100,000 kids getting paralysed every year -- and you'll have this huge setback to global health."
Gates, referring to the economic slowdown in wealthier, donor nations said "it's a very hard time to raise money," but he said he remained confident that enough would be contributed to eradicate the disease.
"In this six-year plan for elimination, we've actually given ourselves some room to deal with setbacks," said Gates, in Ghana to visit health centres and discuss immunisation efforts in a country considered a relative success story for child vaccinations.
"Who knows? There could be an outbreak in any part of Africa, so we need resources to deal with that."
Gates had also been due to visit Nigeria this week, but he cancelled the trip.
The cancellation led to intense speculation in the Nigerian media over whether it was due to President Goodluck Jonathan's recent pardon of a corrupt political ally, which drew sharp criticism from Washington.
Gates' foundation however said the reports were false and that the trip was postponed due to scheduling changes without providing further details.
He maintained that Nigeria was still committed to wiping out polio, though acknowledged that it was the country with the highest number of people who refuse the vaccine.
There have long been claims in Nigeria's mainly Muslim north that polio vaccines are a Western tool to sterilise women.
In 2003, the state of Kano, where February's attacks occurred, had to pause immunisations over the claims.
In the days before the February attacks, a popular radio programme in Kano again hinted at the conspiracy theories, and polio vaccines have been used as a populist political issue in the past.
Gates said Nigeria had in fact expanded its coverage area for immunisations, which had previously been very low.
However, violence in the country's north linked to an Islamist insurgency that has killed hundreds has limited campaigns in some areas.
Gates said security concerns had delayed campaigns in parts of hard-hit Kano, Borno and Yobe states, he said.
"The security situation is certainly a thing that will slow things down, but everybody's still committed to get this thing done," he said.