Guerra, who emerged as a talent last campaign, scored in the 88th minute after Sevilla had lost Loic Badé to a red card eight minutes earlier.
Hugo Duro broke clear and with only the goalkeeper to beat was fouled from behind by Badé, resulting in the defender seeing a direct red.
The striker later helped recover the ball near Sevilla's box before passing to Guerra who slotted home the winner.
Valencia barely avoided relegation last campaign and lost several players in the summer with Samuel Lino, Edinson Cavani, Yunus Musah, Justin Kluivert, Ilaix Moriba and Nico González all leaving.
Valencia coach Rubén Baraja surprised by using central defender Mouctar Diakhaby as a box-to-box holding midfielder.
The move paid off as Diakhaby was found by André Almeida arriving late to the area to score in the 59th minute.
Sevilla striker Youssef En-Nesyri equalised for the hosts in the 69th by heading in a cross by Suso.
Young attacking players Diego López (21) and Fran Pérez (20) also impressed and helped upset Sevilla, last season's Europa League winner.
Morocco goalkeeper Yassine Bounou started for Sevilla amid speculation Real Madrid could be interested in signing him to replace the injured Thibaut Courtois, who will miss several months after tearing a knee ligament on Thursday.
But Sevilla president Pepe Castro said Madrid had not made any moves to sign his club's No.1.
"Sevilla has not received any offers (for Bounou) from any club," Castro said.
Rayo Vallecano forward Randy Nteka scored one goal and helped produce another in a 2-0 win at Almeria.
Rayo took control of the league's inaugural match thanks to two early penalties in the debut of coach Francisco Rodríguez, who replaced the successful Andoni Iraola after he took over Bournemouth in the Premier League.
Midfielder Isi Palazón, Rayo's leading scorer last season, converted a 20th-minute strike after Almeria defender Edgar González fouled Nteka in the area while disputing a ball.
Nteka, who spent the second half of last season on loan at Elche, fired a second spot kick into the corner of the net eight minutes later after Almeria's Sergio Akieme used his arm to block a cross by Nteka in the area.
Rayo flirted with a Europa League berth before finishing 11th last season. This summer they have reinforced their squad with the arrival of central defender Aridane Hernández from Osasuna and left back Alfonso Espino from Cádiz.
Madrid open their season on Saturday at Athletic Bilbao, while Barcelona are at Getafe on Sunday.
