Sevilla separate the giants of Spanish football in second, just a point behind Madrid, after twice coming from behind to edge a seven-goal thriller 4-3 at rock-bottom Osasuna.
However, Real Madrid also have a game in hand over their title rivals.
Barca's visit to the Basque Country was only eight minutes in when Busquets had to be carried off with ankle ligament damage after a dangerous challenge from Gonzalo Escalante that went unpunished.
"The good news about Sergio Busquets is that it doesn't look as serious as we first thought," Barca boss Luis Enrique told Spanish TV station Movistar.
The visitors were briefly unsettled as a fine save from Marc-Andre ter Stegen prevented Adrian Gonzalez giving Eibar a shock lead at the tiny 6,200 capacity Ipurua.
Yet, there was little doubt over the outcome once Denis Suarez, who had replaced Busquets, drilled home his first Barca goal into the far corner from outside the box on the half hour mark.
Neymar missed a one-on-one and Luis Suarez hit the post as Barca squandered a series of chances to kill off the game before half-time.
However, Messi doubled their lead just six minutes into the second-half when he swept home Luis Suarez's cross for his 28th goal in 26 games this season.
Luis Suarez then matched his strike partner as La Liga's top scorer this season with 15 when he robbed Florian Lejeune before slotting home at the near post 22 minutes from time.
Neymar hadn't scored from open play since October, but brought that run to an end by slotting home Aleix Vidal's low cross in stoppage time.
"A positive run of results means everything flows better, the players have more confidence," added Enrique after a fourth straight win. "But we are still far off where we want to be."
Sevilla scored twice in the final five minutes to end Real Madrid's 40-game unbeaten run in all competitions last weekend and have now won five of the seven La Liga games when they have conceded first this season.
"The team did some good things and made mistakes, but from start to finish looked to win the game," said Sevilla boss Jorge Sampaoli. "To finish the first half of the season with a record number of points (42) and be second fills us with excitement for what is to come."
Atletico Madrid lost further ground on the top three as they needed a spectacular Antoine Griezmann equaliser 10 minutes from time to secure a 2-2 draw at Athletic Bilbao, means Diego Simeone's men are now eight points back on Real Madrid.
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