Philippe Coutinho scored from Messi's pass in the second minute to get Barca off to a flying start at Camp Nou on Saturday and the Argentina superstar soon doubled the lead.
But Messi had to be substituted having hurt his right arm in an awkward fall and he could miss Wednesday's Champions League game against Inter, as well as next Sunday's showdown with rivals Real Madrid.
Luis Suarez's second-half penalty and a late strike from Ivan Rakitic secured the points despite consolations from Pablo Sarabia and Luis Muriel, Ernesto Valverde's men moving into first place in the table, with Sevilla third after their four-game winning streak ended.
Despite being on a run of one win in five in all competitions, Barca led inside two minutes with Coutinho bending home a sensational first-time strike to complete a wonderful team move involving Messi and Suarez.
Guilherme Arana struck the post but Messi scored a typically brilliant second for his side in the 12th minute, running on to a superb Suarez pass and cutting inside off the right flank to find the bottom-left corner from 20 yards to record his 25th goal against Sevilla.
Messi, though, was then replaced by Ousmane Dembele after landing heavily on his right arm, Barca's treatment team initially patching him up but finding he could not continue.
Marc-Andre ter Stegen then produced a remarkable double stop before Suarez extended Barca's lead when he sent Tomas Vaclik the wrong way from the penalty spot after he was felled by the goalkeeper.
Sarabia's 79th-minute reply took a vital deflection off former Sevilla defender Clement Lenglet to ruin Ter Stegen's clean sheet, the Germany goalkeeper then making a second double save.
Rakitic added a late fourth with a controlled volley against his old club but Sevilla still had the final say, Muriel bending home a fine finish in added time.
Despite a welcome win, Barcelona will be concerned about Messi's injury ahead of next weekend's Clasico.
Messi major concern
Getting back to winning ways will be a huge relief for Valverde, but Messi's injury gives him another headache. Barca are arguably more reliant on their talisman than ever before and if he is out for any serious length of time, their title aspirations will be severely dented.
