Dutch international Miedema struck in either half after Beth Mead scored the opener, with Rafaelle Souza also getting on the scoresheet in a dominant performance for the hosts.
"We played really well today, we were patient and compact. The fans being here gives us such an energy. Hopefully this is just the beginning," said Mead, who received a standing ovation on her 100th WSL appearance.
Mead, who finished England's victorious Euro 2022 campaign as the tournament's top scorer, had netted twice against Brighton & Hove Albion last weekend and continued her fine form by curling home a sublime goal after five minutes on the clock.
"I still feel like I'm on cloud nine," Mead added. "I don't think it will sink in for a long, long time."
Miedema doubled Arsenal's lead six minutes before the break, slotting past goalkeeper Rebecca Spencer with ease after Spurs carelessly gave away possession deep inside their own half.
Rafaelle found the back of the net with a towering header before Miedema got her second, nodding home Steph Catley's cross after beating Spencer to the ball from close range.
The previous attendance record of 38,262 was set in the reverse fixture in 2019, when Arsenal won 2-0 at the Tottenham Hotspur Stadium in the WSL's first north London derby.
