She told a BBC phone-in that there would be just “more division and uncertainty” if Parliament voted against the agreement next month.
But she declined to say whether the UK would be better off outside the EU, saying only it would be “different”.
A summit of EU leaders to sign off the deal will go ahead on Sunday despite “unresolved” issues over Gibraltar.
Spain is seeking written assurances from the UK that it will be directly consulted over its future trade negotiations with the EU which relate to Gibraltar, a British Overseas Territory.
Its prime minister Pedro Sanchez has said he won’t decide whether to attend Sunday’s summit until these are provided.
He has said his backing for the overall deal cannot be taken for granted although no one country can block the withdrawal agreement on its own at this stage.
The PM is taking to the airwaves to make the case for the agreement, which is opposed by Labour and many Tory MPs.
She told the Emma Barnett Show that her job was to persuade MPs to back her but also to “explain” the merits of the deal to the public.
Asked what would happen if MPs rejected the deal, she said “there would just be more division and more uncertainty”, with people using the opportunity to “stop and frustrate Brexit”.
“From my point of view, personally, there is no question of ‘no Brexit’ because the government needs to deliver on what people voted on in the referendum in 2016,” she said.
“I believe if we were to go back to the European Union and say: Well people didn’t like that deal, can we have another one? … I don’t think they’re going to come to us and say: We’ll give you a better deal.”
Asked if the UK would be better off outside the EU under her deal than staying in, she said that as someone who voted to Remain, she had never said the “sky would fall in” if Brexit happens.
“I think we will be better off in a situation which we’ll have outside the European Union, where we have control of all those things, and are able to trade around the rest of the world,” she told the caller, Michael.
She added: “You say: Are we better off?… actually it’s a different sort of environment, and a different approach that we’ll be taking to things.”
Pressed by Emma Barnett to answer the question, she said “it is going to be different,” before adding: “We can build a better future outside the European Union.”
Mrs May has said a Brexit deal is “within our grasp” after the UK and EU agreed in principle the framework for their future relations – outlining how UK-EU trade, security and other issues would work – on Thursday.
She said she would be touring the country to “explain” the merits of the deal to people who she said wanted to get Brexit over with.
Thursday’s document on future relations, known as the “political declaration”, is not legally-binding but will be the starting point for negotiations on co-operation after the UK leaves. It has been heavily criticised by many MPs for lacking detail.
This is a separate document to the withdrawal agreement – setting out the terms of the UK’s exit from the EU, including the £39bn “divorce bill”, citizens’ rights and the Northern Ireland “backstop” to keep the border with the Republic of Ireland open, if trade talks stall. This agreement will be legally-binding.
Former Brexit secretary Dominic Raab said what was on offer in the political declaration was inferior to EU membership, as it would leave the UK bound by the same rules but without control over them.
He told BBC Radio 4’s Today the current proposal would be “debilitating” for the UK economy and its ability to negotiate independent trade deals would virtually disappear.
The prime minister’s official spokesman denied the deal was worse than EU membership, saying: “This delivers on the vote of the British people.”
But Education Secretary Damian Hinds said he expected the proposed deal to “gain traction” once MPs fully considered the “unattractive” alternatives.
“If we weren’t to pass this deal, I think it becomes rather unpredictable what happens next,” he said.
“There is a risk on the one hand beyond that of no Brexit at all – and there are people trying to thwart Brexit – and there is also a risk of no deal.”
Meanwhile, EU officials are meeting to try to put the finishing touches to both the withdrawal agreement and the political declaration.
The future of Gibraltar and its 30,000 residents, 96% whom voted to remain in the EU in the 2016 referendum, remains a sticking point.
Spain has long contested Britain’s 300 year-rule of the strategically important peninsula.
Gibraltarians overwhelmingly rejected calls for the UK to share sovereignty with Spain in a 2002 vote and there are concerns about how the territory’s political status and economic ties with the Spanish mainland will be affected by Brexit.
Late on Thursday, Spanish Prime Minister Pedro Sanchez struck a combative note in a tweet, saying: “After my conversation with Theresa May, our positions remain far away…. If there are no changes, we will veto Brexit.”
Catherine Barnard, a professor of EU law and employment law at Trinity College, Cambridge, told the BBC that Spain’s room for manoeuvre was limited as the “divorce” document only had to be agreed at EU level by qualified majority voting, meaning 20 of the 27 member states.
“So Spain doesn’t actually have the legal power to block the agreement on the divorce,” she added.
However, any of the remaining 27 countries can block a future EU-UK trade deal so the BBC’s Damian Grammaticas said the EU was reluctant to let its unity fracture by pressing ahead without Spain’s approval.
“What Spain is demanding is a clear statement added to the exit texts that any future agreement between the UK and the EU, such as a trade deal, would not apply to the territory of Gibraltar, unless the UK secured Spain’s explicit consent,” he added.
Fabian Picardo, the chief minister of Gibraltar, said the territory was perfectly happy to have “direct engagement” with Madrid over future trade relations but would not be “dragged” or “vetoed” to the negotiating table when it had concluded the existing agreement in “good faith”.
Speaking on BBC Radio 4’s Today, he warned if Spain sought last-minute changes to the withdrawal deal, that would encourage British MPs and other EU countries unhappy with aspects of the deal to do the same.
The UK government has insisted its Brexit agreement will protect the fishing industry despite claims it is preparing to “sell out” fishermen.
The political declaration says the UK will be an “independent coastal nation” but the SNP has predicted the industry would be used as a “bargaining chip” in the future.