Manchester City need just five points from their remaining three league matches to secure their second Women's Super League title.
Viviane Miedema scored two headers in three first-half minutes to put the visitors on their way to victory.
Kerstin Casparij arrived at the back post to net a third just four minutes after the interval to wrap up the points.
Man City now sit 11 points clear of Manchester United in second, although Chelsea could overtake them tomorrow if they beat Aston Villa.
Arsenal could cut City's lead to five points if they win all three of their games in hand, but they would still require two defeats in City's three final games to stand a chance of catching them.
Story of the Match
Marc Skinner made three changes and a formation switch to the team that narrowly lost 3-2 in the Champions League to Bayern Munich on Wednesday, with Jayde Riviere, Hanna Lundkvist and Simi Awujo coming into the side.
Jess Park moved from the left wing back into the left side of midfield in a 4-4-2 formation, whilst Melvine Malard did the opposite on the right flank.
Man City also made three switches to their side that beat Tottenham 5-2 last weekend, with Ayaka Yamashita, Yui Hasegawa and Aoba Fujino replacing Khiara Keating, Laura Blindkilde Brown and Kerolin.
The hosts were put under the cosh immediately, as Phallon Tullis-Joyce pulled out a smart save to tip Alex Greenwood's close-range shot over the bar; from the resulting corner, a frantic scramble occurred, but the Red Devils were eventually able to clear their lines.
The outcome from a corner 15 minutes later was very different, though, as Miedema leapt above **Lea Schuller**from Greenwood's delivery to score her ninth WSL goal of the season and give City a derby lead.
Within just two minutes, the visitors doubled their advantage through Miedema again, as Casparij's cross found the Dutch striker unmarked for a free header, following a quick counter-attack.
The Citizens, who had just seen Khadija Shaw denied from inside the box, thought they had gone three goals to the good in the 25th minute with Rebecca Knaak heading home, but the referee chalked off the goal for obstruction on the goalkeeper.
The half-time stats were damning for the hosts, with them having just one shot - which was off target - compared to the 10 efforts from their rivals, who had also enjoyed 65% of the ball.
Man United had started on the front foot after the restart, but in the 49th minute, Miedema released Lauren Hemp in space to race forward and put the ball on a plate for Casparij, who tapped the ball in at the back post and put the result beyond their closest challengers.
With a little over an hour gone, Malard was found in space on the right with time to drive at Knaak and get a shot off, but her curling effort didn't bend enough to stop it from sailing past the post.
United's first effort on target came with 74 minutes played, a rather tame header from Malard that Yamashita had no trouble in gathering into her grasp as the Red Devils' hopes of getting something positive faded.
Player of the Match - Kerstin Casparij
Kerstin Casparij bombed up and down the right hand side in her attacking fullback role all afternoon, which was rewarded with both a goal and an assist.
She created three big chances, won 100% of her tackles and delivered seven crosses into the penalty area.