For the second day in a row, it was riders from the break who took the spoils with Clarke (EF Education First-Drapac) using his turn of speed to win a cagey three-up sprint with Bauke Mollema (Trek-Segafredo) and Alessandro De Marchi (BMC).
Molard's (Groupama-FDJ) breakaway exploit saw him leapfrog all of the previous general classification riders to take red with a 61 second lead over Michal Kwiatkowski (Sky). Emanuel Buchmann (BORA-hansgrohe), Simon Yates (Mitchelton-Scott) and Alejandro Valverde (Movistar) round out the top five.
Clarke’s victory heralded a host of firsts - his team's first WorldTour victory since Rigoberto Uran won Stage 9 of the Tour de France last season and the Australian’s first victory since 2016, and his first WorldTour win since the 2012 Vuelta.
The tireless domestique was understandably emotional.
"Just amazing! I've worked so hard since I last won a stage here. And I just couldn't repeat it. It's just taken me so long to get back there and have my stars aligned. Even today I wasn't sure if it was possible.
"I knew I had good legs but when you have a break away with so many riders the cooperation is never very good and as you saw the winning move went on the descent. It was a tricky one to pick but I knew I had good legs and I just had to pray the moves, the ones I was doing were the right ones.
"I grew up on the track since I was 15 and it was just like track racing and I knew that De Marchi's fast but such a long stage it's so hard to sprint after that and even I was cramping when Mollema attacked and I just rode through it. I just backed myself I was so worried they were going to catch us from behind but in that situation you've just go be as cold as ice.
"You've got to be willing to lose to win and so I was and I come out on top."
As Australia's captain at the 2018 UCI Road World Championships later this month, Clarke's form is looking right on the money.
How Stage 5 unfolded
It took more than 37 kilometres before a break was established, with Alessandro De Marchi (BMC) the signature protagonist throughout the action-packed 188.7km from Granada to Roquetas de Mar.
The stage was run fast and hard but the decisive moment came with less than 45 kilometres of road left when De Marchi, Clarke and Mollema combined to take the front.
The trio held more than a minute on a group of counter-attackers and with the bulk of the Sky-led peloton more than five minutes in arrears when the stage reached the final climb up the Alto El Marchal before a long descent to the finish.
Among the early breakaway chasers was Molard, fighting his own race as the virtual leader after starting the stage 3min 46sec behind Kwiatkowski.
Clarke, Mollema and De Marchi spent the final three kilometres jockeying for position as Molard, Davide Villella (Astana) and Floris De Tier (LottoNL-Jumbo) closed in.
Spain's grand tour continues with Stage 6, a 155km flat stage from Huércal-Overa to San Javier Mar Menor that should be one for the sprinters. But hey, it's the Vuelta and with a couple of Cat 3. bumps to conquer on the way, anything could happen.