Barcelona remain unbeaten in La Liga after 23 games, extending their longest run without losing from the start of a campaign.
Alexis Sanchez, 29, was a team-mate of Messi when he plied his trade for Barcelona from 2011 to 2014.
Barcelona are now nine points clear at the top of the table from Atletico Madrid, who beat third-placed Valencia 1-0 at the Wanda Metropolitano.
Messi was pivotal in Barcelona's 1-0 win where he created something out of nothing for Luis Suarez to head home in the 67th minute.
Philippe Coutinho was named on the bench for the first time since his 160 million-euro ($192 million) transfer from Liverpool earlier this month.
Coutinho, dressed in a black shirt dotted with white stars, was in the stands at the Camp Nou for the first time since his 160 million-euro ($192 million) move from Liverpool.
Lionel Messi broke the deadlock from a Jordi Alba assist.
Spanish civil and football authorities have said repeatedly that Catalan secession would end the participation of the region's clubs in the Spanish League.
Harry Kane's second goal took him to 55 for club and country in 2017 -- lifting him above Barcelona's Lionel Messi (54 goals).
Real Madrid remain down in fourth place, but do have a game in hand on their rivals.
Matias Messi, older brother of Barcelona and Argentina star Lionel, has been sentenced to house arrest in Argentina for possession of a weapon, a prosecutor said Monday.
Cristiano Ronaldo, who also won the FIFA Men's Player of the Year award in October, added the 2017 Ballon d'Or to his previous wins in 2008, 2013, 2014 and 2016.
Argentina endured a torrid qualifying campaign in South America's CONMEBOL group, only securing a World Cup place in the last match against Ecuador in October
Barcelona's 30-year-old Argentinian superstar won the coveted award from 2009 to 2012 and in 2015. Portugal's Ronaldo, who is 32, took the honours in 2008, 2013, 2014 and last year.
Barcelona's slip-up is a boost for Real Madrid and Atletico Madrid, who can close to within six points with victories over Athletic Bilbao and Real Sociedad respectively later on Saturday.
Just a second slip up from Barcelona this La Liga season allowed Real Madrid and Atletico Madrid to close to within eight points of the leaders.
Lionel Messi ended months of speculation when finally putting pen to paper to extend his contract with Barcelona until 2021.