The Italian midfielder, who returned to action earlier this season after serving a 10-month worldwide ban for breaching betting regulations while at AC Milan, has gradually become a key figure in Eddie Howe's side.
His latest contribution could prove crucial in Newcastle's push for a top-four finish.
Newcastle took the lead through Alexander Isak, but Brentford's Bryan Mbeumo equalised, setting up a tense finale. With 16 minutes remaining, Tonali struck from a near-impossible angle past Brentford goalkeeper Mark Flekken.
The 24-year-old later admitted the goal was intended as a cross, but it was enough to hand Newcastle all three points.
The victory moves the Magpies just one point behind fourth-placed Manchester City, with a game in hand. With last month's Carabao Cup triumph still fresh, Newcastle are now setting their sights on securing a Champions League spot.
"I am happy for the team and happy for this win. It is three points that can help us come back to the Champions League. This is a massive win for us. We need to win every game at St James' Park," said Tonali.
"Now we play only (to be among) the first five teams, for the Champions League. It is a little bit tough, but we are lucky because there are five teams in the Champions League this season.
"The team is a little bit free, so it is much better for me and for the fans. Now we have nine finals to get back into the Champions League."
Anthony Elanga's early strike against his former club handed Nottingham Forest a massive 1-0 win over Manchester United, further cementing their remarkable season and boosting their Champions League ambitions.
Mikel Arteta has confirmed that Bukayo Saka is back to full fitness after a three-month injury absence, with the Arsenal winger set to make his long-awaited return to action.
Arsenal could be handed a major boost ahead of their Champions League quarter-final against Real Madrid, with Kylian Mbappe reportedly among the players 'at risk of being banned' by UEFA.
Arsenal have received a major boost ahead of their upcoming clash with Real Madrid as Bukayo Saka posted an encouraging update on his fitness.
