The University of Exeter has "raised its game" even further and been named University of the Year by The Sunday Times.
The leading Devon institute bettered last year's narrow defeat by the University of Bath to claim top spot, climbing from ninth to seventh in the national rankings, the highest position since the guide launched 15 years ago.
Plymouth University – the biggest in the South West and a Queen's Anniversary prize winner for its work in the marine and maritime sector – has ascended a dozen places up the latest order of merit and edged into the top 50 for the first time.
Elsewhere in the Westcountry, University College Plymouth St Mark and St John, known as Marjon, and Cornwall's Falmouth University slipped out of the top 100, sitting in 102nd and 104th position respectively, out of a total of 126.
Exeter broke into the elite top 10 for the first time last year, after the 64-page guide placed greater emphasis on the student experience and graduate outcomes.
Sir Steve Smith, vice-chancellor, said he takes student views seriously and personally read all 4,260 pieces of written feedback from last year's final-year undergraduates.
He said: "We are engaged with our students, but that does not mean we ask them what they want and then go and do it. They put their views forward and we put ours. It's a very grown-up conversation – students are our lifeblood."
The rest of the top ranking universities will be revealed in The Sunday Times University Guide 2013 tomorrow.
Cambridge and Oxford retain their status as the leading universities. But the greater South West can now boast the next best seat of learning after the University of Bath, best in the region, moved up from fifth to third nationally.
Alastair McCall, editor of the guide, said: "Exeter's success was "richly deserved", and timed perfectly as new students to the university begin to enjoy the new £380m investment in facilities.
"A key player regionally, nationally and internationally, it has responded to the challenge of £9,000 fees by raising its game more than any other university," he added.
"More than four in five leave with a first or 2:1 and very few drop out – it is not hard to see why."
Plymouth University vice-chancellor Professor Wendy Purcell said joining the top 50 "rounds off an amazing 150th anniversary year".