The Yellow Submarine, who won the Europa League last term, lost on penalties to Chelsea in the Super Cup on Wednesday, but this will be Granada's first competitive fixture in three months.
Villarreal won 15, drew 13 and lost 10 of their 38 La Liga matches last season to finish seventh, three points behind sixth-place Sevilla and some 19 points behind Sevilla in fourth position.
The Yellow Submarine will compete in the group stage of the 2021-22 Champions League, though, courtesy of their win over Manchester United in last season's Europa League final; the two teams could not be separated at the end of 120 minutes, but Unai Emery's side won 11-10 in the penalty shootout.
Villarreal also played out a 1-1 draw with Chelsea in the UEFA Super Cup on Wednesday night, but they lost the shootout 6-5 on this occasion, with Aissa Mandi and Raul Albiol missing their spot kicks against the Blues.
Villarreal will be expecting to push closer to the top four this term, and it will be fascinating to see how the team perform in their first Champions League group-stage campaign since 2011-12.
Granada, meanwhile, secured a third straight season at this level of football courtesy of finishing ninth last season, with 13 wins, seven draws and 18 defeats seeing them collect 46 points.
The Andalusian side have finished seventh and ninth since returning to the top flight, and they are now under the leadership of former Spain boss Robert Moreno, who has replaced Diego Martinez at the helm.
Moreno's team have played five friendlies this summer, recording three victories, including back-to-back wins over Linense and Malaga in their final two pre-season fixtures.
Granada have not actually beaten Villarreal in Spain's top flight since 2014, but the corresponding match during the 2020-21 campaign ended in a 2-2 draw.
Pau Torres, who is currently being strongly linked with a move to Tottenham Hotspur, has been given the early stages of the season off due to his busy summer with Spain, so new signing Mandi could start at the back.
Villarreal possible starting lineup:
Asenjo; Foyth, Mandi, Albiol, Pedraza; Pino, Trigueros, Capoue, A Moreno; G Moreno, Dia
Granada possible starting lineup:
Escandell; Foulquier, Duarte, Sanchez, Neva; Puertas, Montoro, Gonalons, Milla, Machis; Suarez
We say: Villarreal 2-1 Granada
Granada are certainly a team to be taken seriously at this level of football, and it would not be a surprise to see them claim another top-half finish this term. Wednesday's Super Cup fixture would have been valuable for Villarreal in terms of building fitness, though, and we can see the home side edging out a victory in this contest to put an early three points on the board.