The Whites made the short trip to Leicestershire for a Saturday lunchtime meeting with La Liga's sixth best side at Loughborough University.
Manuel Pellegrini's men are bound for the Europa League in a few weeks and gave Marcelo Bielsa's men a good run around - edging out United 3-2 in a closely-fought contest in front of around 3,000 supporters.
Leeds went ahead through Patrick Bamford after just six minutes as United's number 9 glanced home a cross from summer signing Junior Firpo.
Betis, though, hit back four minutes later through Aitor before the Spanish tourists took the lead thanks to a low effort from Borja Iglesias.
Youssouf Sabaly then added a third before the hour mark as the game ebbed and flowed, leaving Leeds with work to do as the clock ticked down.
Mateuz Klich cut the lead back to one two minutes later to give the game life once again with the Pole punishing a mistake at the back to fire into the net.
Despite United's best efforts, Bielsa's men failed to level late on even with good chances for Rodrigo and winger Helder Costa.
Shackleton - who was an early substitute for injured defender Diego Llorente - was left pleased at full-time as Leeds continued to build towards an all-important opening top flight game against Manchester United on August 14.
"It was tough, particularly at stages in the second half," Shackleton reflected post-match.
"They kept the ball well and we struggled to recover the ball back high up the pitch which we always try to do. They played out well which gave us a bit of a run around at times but we kept going and I thought we dealt with it better.
"They're a good side, good on the ball. They're brave and they like to receive it in dangerous areas and they're confident. Like I said, they managed to play out well at times and that's when we struggled with the press."
Asked about the late physicality which crept into the game - notably Nabil Fekir's kick out at Pascal Struijk - he said: "As players it is as if it's a league game. We worked hard, we ran around and we gave it our all."
Shackleton featured for the entire match at Championship side Blackburn Rovers on Wednesday night and picked up more valuable minutes against Betis.
The Thorp Arch academy product filled in at right-back once again and is enjoying the game time he's been afforded in pre-season so far.
"It's good getting minutes," the 21-year-old said.
"[I had] 90 the other night and about 70 minutes today, so it's been good to get minutes along with that match sharpness back. We want to get up to 100 per cent so we're ready to go in two weeks time."