Walton, the rising Brisbane star who's moved to No.3 in the Australian rankings, had hoped to replicate his shock win over Medvedev at the Cincinnati Open in August -- the biggest win of his career -- in Thursday's round-of-16 rematch in the Kazakh hard-court event.
But the three-time Australian Open finalist Medvedev has been rediscovering some of his best form of the season in the last couple of weeks, as Alex de Minaur could attest last week when he played a fine quarter-final at the Shanghai Masters only to be outstayed by the rejuvenated 29-year-old.
Walton again gave the Russian plenty of trouble in their one hour 45 minute duel, losing the first set after suffering one break of serve at 5-5, and then hitting back to take control of the second at 4-1.
The Queenslander will perhaps look back on the five break points he earned but squandered on Medvedev's next service game as the key passage of play, with the Russian going on to hold, battle back in the set and take it to a tiebreak which he dominated.
"It was a very tough match. The game at 1-4 was crucial because then I managed to break back and get back into my rhythm, so I am pleased to have defeated a tough opponent," said Medvedev.
He's been left delighted by his resurgence on the tour's Asian swing, having reached the semi-finals in Shanghai and Beijing and now having picked up eight wins in his past 10 matches.
Walton's reward for another decent week's work in Kazakhstan could be another career-high placing when the next rankings are published, as he currently stands at a new best of No.73 in the live standings.
The No.2 seed Medvedev will next play Fabian Maroszan in the quarter-finals, after the Hungarian knocked out American Brandon Nakashima.
Walton's Australian compatriot Aleksandar Vukic also departed the tournament, 6-3 6-2 at the hands of power-packed American No.6 seed Alex Michelsen.
That leaves qualifier James Duckworth as the only Aussie still standing in the singles, as he prepares to face third seed Flavio Cobboli in the quarters on Friday.
Meanwhile in China, Alja Tomljanovic learned her quarter-final opponent at the WTA's Ningbo Open will be the formidable Elena Rybakina, the former Wimbledon champion who defeated Dayana Yastremska 6-4 6-7 (6-8) 6-3.
