An own goal by centre-back Ruben gave the hosts an early lead but two goals by Kike Sola within 10 minutes after half-time put Jose Mendilibar's side in the lead, before Miguel De Las Cuevas scored his first goal for the club to make sure of the points.
Patrick Ebert made his first appearance for Valladolid in over 10 weeks after finally recovering from a thigh injury, while Osasuna were boosted by the return of top scorer Sola, who missed their last league match, a 2-0 defeat at home to Atletico Madrid.
There was little to choose between the two sides in the opening exchanges, but the deadlock was broken by a calamitous own goal.
Osasuna goalkeeper Andres Fernandez came out to gather a straightforward cross from the left hand side and faced no pressure from Valladolid players, but it was his own team-mate Ruben who went for the ball and headed it into his own net.
The visitors responded well to going behind and created several attempts to find an equaliser, while Valladolid also searched out a second goal, making for an end-to-end first half.
Fernandez did well to keep out efforts from Oscar and Manucho, while Osasuna's Alejandro Arribas nearly scored another own goal.
At the other end, Nino squandered a great chance to level on the stroke of half-time, but shot straight at Dani Hernandez from close range.
Alberto Bueno was inches away from doubling their lead right after the re-start but failed to get on the end of a cross, and minutes later the score was level, due to another error.
Hernandez spilled a shot from De Las Cuevas which sat up perfectly for Sola, who dived forward to head home.
Ten minutes later Sola was on the score-sheet again. Hernandez came out to punch a corner but it was headed back towards goal by Francisco Silva and Sola, with his back to goal just outside the six-yard box, headed the ball past a stranded Hernandez and into the net.
Valladolid brought on Omar Ramos in search of an equaliser but the substitution had little effect and Osasuna extended their lead shortly after. De Las Cuevas robbed the ball on the halfway line and then surged towards goal unchallenged and coolly slotted past Hernandez.
The third goal killed off any hopes of a Valladolid revival and Osasuna could have scored more goals, but the Navarrans, nor the 500 fans that travelled to the Jose Zorilla stadium to cheer them on, will not be complaining about the result, which was just their third win away from home all season but puts them seven points clear of the relegation zone.
Valladolid remain 11 points clear of the drop zone but may be concerned by their home form - they have not won in front of their own fans for over two months.