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Manchester United's top-four hopes were dented as they were held to a 0-0 draw by relegation-threatened Watford.
Mohamed Salah and Luis Diaz allowed Juergen Klopp's Liverpool to close the gap to six points at the top, and they also have a game in hand over City.
Ronaldo, without a goal since December and dropped to the bench by interim manager Ralf Rangnick in some recent matches, answered his critics five minutes after half-time with a superb finish.
Manchester United's troubles continued as a 1-1 draw with Southampton further damaged their top-four hopes.
Klopp's team posted 3-1 win over Crystal Palace.
Leeds United pulled eight points clear of the relegation zone with a 3-1 win over Burnley.
With Liverpool losing at Leicester City on Tuesday and Chelsea held by Brighton and Hove Albion on Wednesday, City have seized complete control of the title race.
Chelsea slipped to third spot with 33 points from 15 games, one point behind Liverpool and two behind Manchester City.
Chelsea proved far too strong for Newcastle United as Reece James struck twice to fire the Premier League leaders to a 3-0 win at St James' Park.
Chelsea beat Aston Villa 3-0 for their 600th Premier League victory to move joint top of the standings alongside Manchester United.