Columbus topped the ranking by Forbes, edging past New Orleans and Hartford, Connecticut and their surrounding areas. Cincinnati and its suburb of Middletown came in fourth, just ahead of Providence and neighboring towns in Rhode Island.
With a population of 1.8 million, Columbus scored high marks for its higher than average salaries for women, who make up 44 percent of the city's workforce.
The city also boasts a jobless rate of 5.7 percent, much lower than the national 7.8 percent, and good schools and childcare, according to Forbes.
"Pairing the excellent unemployment rate with an affordable but impressive quality of living makes the city an attractive locale for savvy working moms," Forbes said.
Another Ohio city, Cleveland, came in seventh, while Buffalo, New York, which topped the list last year, dropped to eighth place.
New Orleans' affordable childcare and higher per-pupil spending helped to propel it into the top 10. Families in the city, known as the Big Easy, pay about $5,900 annually for childcare, while New Yorkers have to budget more than double that amount - roughly $13,000.
Although working mothers are paid among the highest salaries in Boston and Washington D.C., both cities dropped out of the top 10 this year because the cost of living and childcare are above average, according to Forbes.
And like New York, where people spend as much as 80 minutes commuting each day, workers in Boston and the nation's capital also have lengthy trips back and forth to work.
To compile the list, Forbes ranked the cities on job opportunities and earning potential, cost of living, commuting times, cost of childcare, quality of schools, crime rates and healthcare.
It used data from various sources including the U.S. Bureau of Labor Statistics, the FBI Uniform Crime Report, the National Association of Child Care Research and Referral Agencies and the ACCRA Cost of Living Index.