Boris Johnson has accused Welsh Labour of "separatism" on a Bank Holiday Monday visit to Wales.
The UK prime minister was campaigning in Barry, Vale of Glamorgan, as parties began the last week of the Welsh Parliament election campaign.
Mr Johnson said voters wanted to see politicians working together to beat the pandemic.
But Welsh Labour leader Mark Drakeford it was Mr Johnson who was encouraging support for Welsh independence.
On a visit to Swansea, Wales' first minister said there would be a mandate for more powers in Cardiff if voters backed a majority supporting more devolution.
Meanwhile, Plaid Cymru said a pro-independence government in Wales would have more leverage over Westminster.
Voters go to the polls in the Senedd elections on Thursday.
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Mr Drakeford, who has been Welsh Labour leader since 2018, is opposed to independence, unlike Plaid Cymru's Adam Price who has made it a key part of his campaign.
Both parties also argue for more issues in Wales to be in the control of ministers in Cardiff rather than London, such as policing and justice.
"I don't think the people of this country are obsessing right now about further constitutional change," Mr Johnson, who was visiting the Conservative party office in Barry town centre, told BBC Wales.
"I think what they want to see is politicians working together to beat the pandemic."
The prime minister said he was a "believer in devolution" but he wanted to see "people using their powers effectively".
But he added that both Plaid Cymru and Labour "are obsessed with the constitutional issues, trying to go for more separatism. I don't think that's the right way forward."
"I think we should be working together," he said.
"I think we should have a situation which people can be proudly emphatically Welsh, but also see the merits and the beauty of doing things together."
Mr Drakeford said there could be a mandate for further powers to come to Cardiff if a pro-devolution majority is returned to the Senedd after the election.
"It could well be that they will be a majority of voters in Wales supporting parties who want to see devolution strengthened and entrenched," he said.
"And that's a message that the UK government really will need to heed.
"I often think that the prime minister is the greatest recruiting sergeant for people who believe that Wales will be better off outside the United Kingdom.
"I hope the prime minister would act in ways that reinforce those of us who make the positive case for the union rather than undermining us".
Asked about his remarks captured in a S4C documentary when he called the PM "awful" after a Cobra meeting, Mr Drakeford said: "My views of the prime minister are a good deal kinder than many people who have worked in Downing Street with him".
Meanwhile, Mr Price, Plaid's leader since 2018, said the Welsh government would have "greater leverage" in London if it was led by a pro-independence party.
"That's exactly what we will get from the election of a Plaid Cymru government," he said.
"A strong Welsh Government with a strong voice able to negotiate a far better deal than anything we've seen under a Labour government over the last 22 years."
Mr Price, who was campaigning in Ystrad Mynach in the constituency of Caerphilly, said there had been "one economic plan" from Welsh Labour.
"It's all been about just looking to salvation from companies coming in from outside, that's not going to build the economic foundation for the future.
"We've got to shift the focus from just relying on foreign-owned companies coming in for a while - we've got to invest in our own homegrown businesses.
Welsh Labour said this was a "false choice".
Mr Drakeford added: "I absolutely think that we need to invest in indigenous companies and to grow indigenous companies that then stay rooted here in Wales.
"But a Labour government is never going to turn our back on people who want to come and invest in Wales from elsewhere."
Jane Dodds, the leader of the Welsh Liberal Democrats, spent the day campaigning in the Wrexham area of north Wales.
She said her party had a "big message" on Covid recovery in the final few days of the campaign and that was putting the economy, mental health and the planet "first".
The Liberal Democrats had one Senedd seat at the last election. Its former occupant, Brecon and Radnorshire's Kirsty Williams, is quitting the Welsh Parliament after 22 years.
Ms Dodds denied that her party was facing a fight for survival in mid-Wales. "Every single vote important," she said, "it doesn't matter where it is."
WALES ELECTION: THE BASICS
What's happening? On 6 May, people will vote to elect 60 Members of the Senedd (MSs). The party that can command the support of a majority of MSs will form the Welsh government. Find out more here.
What powers does the Senedd have? MSs pass laws on aspects of life in Wales such as health, education and transport - and have some tax powers.
The Welsh Liberal Democrats said they were focusing on the "health recovery".
Leader Jane Dodds, who is in Llanidloes and Wrexham on Monday, said: "We owe the NHS so much, we are pledging a proper pay rise for front-line nurses as well as a commitment to pay all social care staff the real living wage.
"Welsh Lib Dems understand the stress and pressure that our NHS heroes are under and we want to support put healthcare staff, not just through a pay rise but by investing in new staff and new technology to benefit both staff and patents," she said.