Experienced opener Tammy Beaumont's unbeaten 150 - her 10th century at this level - powered England to a total of 320-8 in their 50 overs.
It was far too much for a fledgling Ireland team, who were bowled out inside 17 overs, with England captain Kate Cross taking 3-8 and new-ball partner Lauren Filer 3-10.
Ireland opener Una Raymond-Hoey's 22 was the only double-figure score of an innings that ended with England 2-0 up in a three-match series.
England's largest women's ODI win in terms of runs was achieved by a mainly second-strong team, with the majority of their T20 World Cup squad not involved.
"Cricket is a sport of ups and downs, and today was definitely a down day," Ireland captain Gaby Lewis, one of three home batters out for a duck, told the Cricket Ireland website.
"We are a very young squad, we're learning on the go. We've got three bowlers under the age of 19, it's very hard on them."
Beaumont, however, insisted: "I found it tough early on and Ireland were bowling tight lines with a slower pace on the pitch."
