England set up a Grand Slam decider against France at Twickenham next weekend with a 59-7 rout of Scotland on Saturday.
Earlier, France were far less impressive as they were forced to come from 21-12 behind at half-time to beat Italy 34-21 for their fourth win of the championship.
England are big favourites to secure a seventh consecutive Women's Six Nations title after extending their winning run to 24 matches with a nine-try display at Leicester's Welford Road.
Kelsey Clifford, Marlie Packer, captain Zoe Aldcroft, MacDonald, Abbie Ward and Lark Atkin-Davies all went over to put England 42-0 up at half-time.
MacDonald touched down for her second try after the break and although Scotland responded through centre Lisa Thomson's score, Claudia Dow had the crowd out of their seats with her first try before she completed the scoring.
"It was awesome," said Packer. "You can't take for granted playing for England.
"The calibre of players we have got coming through, players who are training and not even on the bench who are so good. It shows the depth we have got."
France were the last side to beat England in the Six Nations back in 2018.
But they will need a much-improved display to spring a surprise on April 26 after needing two late tries to see off Italy.
Marine Menager and Alexandra Chambon finally put distance between the visitors and their resilient hosts.
"We said at half-time do not lose our heads," said Menager, whose twin sister Romane scored a try earlier in the second half.
"The key was not to panic, to slowly regain a foothold in the match.That is what we did."
France scrum-half Pauline Bourdon Sansus said people may write off their chances, but they would go to England full of belief in themselves.
"We will play our game, we have nothing to lose," she said.
"We have been chasing this prize since 2018, and we want to end that drought."