Bangor and Aberystwyth universities are planning a "strategic alliance" as institutions around Wales look to work more closely.
Bangor Vice-Chancellor John Hughes said they would become "very close partners" but were too far apart to merge.
Aberystwyth University said it was committed to broadening a partnership with Bangor.
Education Minister Leighton Andrews has challenged universities to "adapt or die".
In December, Mr Andrews said universities would only be permitted to charge increased tuition fees from September 2012, upon which their survival would depend, if they could demonstrate they intended to collaborate more closely.
The Higher Education Funding Council for Wales (HEFCW) subsequently published plans to halve the number of universities by 2013.
Last week, a decision to form a "super university" in Wales was also announced.
University of Wales Institute Cardiff (Uwic), Swansea Metropolitan University and Trinity Saint David in Carmarthen and Lampeter will merge as The University of Wales.
Both Bangor and Aberystwyth universities already work together on various projects.
"What we're currently doing and the steer we've been given from the department and HEFCW is that we should be forming a strategic alliance with Aberystwyth but short of a merger," said Prof John Hughes.
"We will build on what is already a very fine, trusting relationship with Aberystwyth and this partnership will be built into the governance of the two institutions so we seem to be two very close partners, the geographical implications of merging two institutions two and a half hours apart are just not sensible."
Prof Hughes said the biggest challenge was funding and "getting through the massive change that's going to take place over the next few years".
He added: "I think we're well placed to do that but it is going to be a significant challenge and it is going to require some change.
"What's coming in 2012 is probably the biggest change at this university since the Second World War and I don't think anybody has really yet fully understood just exactly what the impact will be in terms of students, staff and the institution."
Aberystwyth Vice-Chancellor Prof Noel Lloyd said: "The relationship between the two universities is excellent and Aberystwyth University is committed to broadening and deepening the partnership with Bangor University.
"Professor John Hughes and I are working together to take this forward. Our partnership is developing in a number of areas: the Aberystwyth-Bangor Skills Centre, for example, and we have recently seen the establishment of the Mid and North Wales Centre for Teacher Education."
Aberystwyth is 80 miles (129 kms) from Bangor.